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sag  (Tocris)


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    Tocris sag
    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed <t>to</t> <t>recombinant</t> human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and <t>SAG</t> (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Sag, supplied by Tocris, used in various techniques. Bioz Stars score: 93/100, based on 58 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/ac2+26/pmc13032639-139-16-17?v=Tocris
    Average 93 stars, based on 58 article reviews
    sag - by Bioz Stars, 2026-06
    93/100 stars

    Images

    1) Product Images from "Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms"

    Article Title: Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms

    Journal: Molecular Cancer

    doi: 10.1186/s12943-026-02611-y

    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed to recombinant human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Figure Legend Snippet: Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed to recombinant human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test

    Techniques Used: Derivative Assay, Activation Assay, Inhibition, Fluorescence, Staining, Recombinant, Expressing, Quantitative RT-PCR, Control, Labeling, Quantitation Assay, BrdU Incorporation Assay

    HH signaling regulates the growth of GFAP ΔMen1 and Sox10 ΔMen1 pancreatic NET tumoroids. A Phase contrast and ( B ) fluorescence images of PanNET tumoroids from Sox10-Cre; Men1 FL/FL ; LSL-tdTomato mice. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure PanNET tumoroid growth in the presence of HH pathway agonists or ( D ) inhibitors of the canonical and ( E ) non-canonical HH signaling pathways. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates in two unique mouse PanNET tumoroid lines). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F BrdU incorporation was used to measure tumoroid proliferation in GFAP ΔMen1 and Sox10 ΔMen1 PanNET tumoroids after 72 h treatment. ( n = 4). ** = p < 0.01, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. G Relative fold-change in Chga mRNA levels in PanNET tumoroids following 72 h treatment. ( n = 5). H Western blot analysis of HH pathway proteins in PanNET tumoroids after 72 h treatment. I Quantitation of SHH protein expression normalized to beta-actin and DMSO vehicle control from the western blot analysis in panel ( H ). ( n = 3). J Western blot analysis and ( K ) associated quantitation of phosphorylated and total ERK and AKT growth pathways in PanNET tumoroids after 72 h treatment. ( n = 3). * = p < 0.05, ** = p < 0.01, *** = p < 0.001 by Kruskal-Wallis test
    Figure Legend Snippet: HH signaling regulates the growth of GFAP ΔMen1 and Sox10 ΔMen1 pancreatic NET tumoroids. A Phase contrast and ( B ) fluorescence images of PanNET tumoroids from Sox10-Cre; Men1 FL/FL ; LSL-tdTomato mice. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure PanNET tumoroid growth in the presence of HH pathway agonists or ( D ) inhibitors of the canonical and ( E ) non-canonical HH signaling pathways. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates in two unique mouse PanNET tumoroid lines). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F BrdU incorporation was used to measure tumoroid proliferation in GFAP ΔMen1 and Sox10 ΔMen1 PanNET tumoroids after 72 h treatment. ( n = 4). ** = p < 0.01, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. G Relative fold-change in Chga mRNA levels in PanNET tumoroids following 72 h treatment. ( n = 5). H Western blot analysis of HH pathway proteins in PanNET tumoroids after 72 h treatment. I Quantitation of SHH protein expression normalized to beta-actin and DMSO vehicle control from the western blot analysis in panel ( H ). ( n = 3). J Western blot analysis and ( K ) associated quantitation of phosphorylated and total ERK and AKT growth pathways in PanNET tumoroids after 72 h treatment. ( n = 3). * = p < 0.05, ** = p < 0.01, *** = p < 0.001 by Kruskal-Wallis test

    Techniques Used: Fluorescence, Protein-Protein interactions, Control, BrdU Incorporation Assay, Western Blot, Quantitation Assay, Expressing

    GFAP ΔMen1 DNETs and jejunal NETs are sensitive to HH pathway activation and inhibition. A Phase contrast and ( B ) fluorescence images of DNET tumoroids from a GFAP-Cre; Men1 FL/FL ; LSL-tdTomato mouse. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure DNET tumoroid growth in the presence of HH pathway inhibitors. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates using one mouse DNET tumoroid line). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. D Relative BrdU incorporation in a second GFAP ΔMen1 DNET tumoroid line and ( E ) a jejunal tumoroid line (J-NET) after 72 h treatment. ( n = 4). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F Western blot analysis of SHH, ERK, and AKT growth pathways in J-NET tumoroids after 72 h treatment. G Western blot quantitation of SHH and ( H ) phosphorylated and total ERK and AKT proteins normalized to GAPDH and DMSO vehicle control. ( n = 3). * = p < 0.05 by Kruskal-Wallis test. I Crystal violet staining of mouse STC-1 SI-NET cells after 48 h treatment with agonists and inhibitors of the HH signaling pathway. J BrdU incorporation in STC-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Figure Legend Snippet: GFAP ΔMen1 DNETs and jejunal NETs are sensitive to HH pathway activation and inhibition. A Phase contrast and ( B ) fluorescence images of DNET tumoroids from a GFAP-Cre; Men1 FL/FL ; LSL-tdTomato mouse. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure DNET tumoroid growth in the presence of HH pathway inhibitors. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates using one mouse DNET tumoroid line). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. D Relative BrdU incorporation in a second GFAP ΔMen1 DNET tumoroid line and ( E ) a jejunal tumoroid line (J-NET) after 72 h treatment. ( n = 4). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F Western blot analysis of SHH, ERK, and AKT growth pathways in J-NET tumoroids after 72 h treatment. G Western blot quantitation of SHH and ( H ) phosphorylated and total ERK and AKT proteins normalized to GAPDH and DMSO vehicle control. ( n = 3). * = p < 0.05 by Kruskal-Wallis test. I Crystal violet staining of mouse STC-1 SI-NET cells after 48 h treatment with agonists and inhibitors of the HH signaling pathway. J BrdU incorporation in STC-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test

    Techniques Used: Activation Assay, Inhibition, Fluorescence, Control, BrdU Incorporation Assay, Western Blot, Quantitation Assay, Staining



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    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed <t>to</t> <t>recombinant</t> human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and <t>SAG</t> (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
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    Tocris ac2 26
    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed <t>to</t> <t>recombinant</t> human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and <t>SAG</t> (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Ac2 26, supplied by Tocris, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    ac226  (MedChemExpress)
    93
    MedChemExpress ac226
    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed <t>to</t> <t>recombinant</t> human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and <t>SAG</t> (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Ac226, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    ac2 26  (MedChemExpress)
    93
    MedChemExpress ac2 26
    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed <t>to</t> <t>recombinant</t> human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and <t>SAG</t> (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Ac2 26, supplied by MedChemExpress, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    annexin a1 mimetic peptide  (Tocris)
    93
    Tocris annexin a1 mimetic peptide
    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed <t>to</t> <t>recombinant</t> human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and <t>SAG</t> (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test
    Annexin A1 Mimetic Peptide, supplied by Tocris, used in various techniques. Bioz Stars score: 93/100, based on 1 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
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    Image Search Results


    Schematic overview of the experimental workflow for generating ANXA1-knockdown CHO cell lines and AC2-26 inhibitor treatment. (A) Generation and validation of ANXA1-knockdown cell lines for rADM antibody production. (B) AC2-26 inhibitor treatment in low-producer CHO cells (ADM-14) and subsequent rADM expression analysis.

    Journal: Synthetic and Systems Biotechnology

    Article Title: Leveraging ANXA1 to enhance recombinant protein yields in CHO cells: A UPR-Mediated bioprocessing approach

    doi: 10.1016/j.synbio.2025.12.001

    Figure Lengend Snippet: Schematic overview of the experimental workflow for generating ANXA1-knockdown CHO cell lines and AC2-26 inhibitor treatment. (A) Generation and validation of ANXA1-knockdown cell lines for rADM antibody production. (B) AC2-26 inhibitor treatment in low-producer CHO cells (ADM-14) and subsequent rADM expression analysis.

    Article Snippet: On day 3 of suspension culture, the small molecule inhibitor AC2-26 (Topscience Co., Ltd., China) was added [ ], using DMSO (Solarbio Life Sciences, China) as the solvent control.

    Techniques: Knockdown, Biomarker Discovery, Expressing

    AC2-26 effect on ADM-14 CHO cells. (A) Cell density/viability under AC2-26 treatment (n = 3). (B) rADM expression by Western blot with quantification (n = 3). (C) ANXA1 mRNA/protein comparison (n = 3). Quantification was performed using ImageJ (for Western blot densitometry) and GraphPad Prism 10 (for statistical analysis). (∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, ∗∗∗∗ P < 0.0001). n: represents independent biological replicates.

    Journal: Synthetic and Systems Biotechnology

    Article Title: Leveraging ANXA1 to enhance recombinant protein yields in CHO cells: A UPR-Mediated bioprocessing approach

    doi: 10.1016/j.synbio.2025.12.001

    Figure Lengend Snippet: AC2-26 effect on ADM-14 CHO cells. (A) Cell density/viability under AC2-26 treatment (n = 3). (B) rADM expression by Western blot with quantification (n = 3). (C) ANXA1 mRNA/protein comparison (n = 3). Quantification was performed using ImageJ (for Western blot densitometry) and GraphPad Prism 10 (for statistical analysis). (∗ P < 0.05, ∗∗ P < 0.01, ∗∗∗ P < 0.001, ∗∗∗∗ P < 0.0001). n: represents independent biological replicates.

    Article Snippet: On day 3 of suspension culture, the small molecule inhibitor AC2-26 (Topscience Co., Ltd., China) was added [ ], using DMSO (Solarbio Life Sciences, China) as the solvent control.

    Techniques: Expressing, Western Blot, Comparison

    Ac2-26 administration treats established nephritis in MRL/ lpr mice. (A) Ac2-26 treatment protocol for MRL/ lpr mice. Ac2-26 (2 mg/kg) or PBS treatments were administered i.p. every other day from weeks 10 to 20. n = 6 per group. (B) Levels of anti-dsDNA antibodies in different groups at 10 weeks and 20 weeks (n = 6). (C) Serum creatinine levels in different groups at 10 weeks and 20 weeks (n = 6). (D) Urinary protein/creatinine ratios in different groups at 10 weeks and 20 weeks (n = 6). (E) Representative sections of renal tissue stained with H&E, Masson's trichrome, PAS, and PASM staining and semi-quantitative evaluation of glomerulonephritis at 20 weeks. Bars = 50 μm. (F) Representative photomicrographs and quantitative analysis of Sirius Red staining at 20 weeks. n = 5 per group. Bars = 50 μm. (G) Immunohistochemical staining and quantitative analysis of F4/80 at 20 weeks. n = 5 per group. Bars = 50 μm. (H) Immunohistochemical staining and quantitative analysis of osteopontin (encoded by Spp1 ) at 20 weeks. n = 5 per group. Bars = 50 μm. (I) Representative photomicrographs and quantitative analysis of Oil Red O staining at 20 weeks. n = 5 per group. Bars = 50 μm. (J) Immunohistochemical staining and quantitative analysis of Fabp4 at 20 weeks. n = 5 per group. Bars = 50 μm. Data analyses were performed by Student's t -test for two groups. * P < 0.05; ** P < 0.01; *** P < 0.001. i.p.: intraperitoneally; HE: hematoxylin-eosin; PAS: periodic acid-Schiff; PASM: periodic acid-silver methenamine.

    Journal: International Journal of Biological Sciences

    Article Title: ANXA1-mediated mTOR/FABP4 Inhibition Drives Antifibrotic Macrophage Reprogramming in Lupus Nephritis

    doi: 10.7150/ijbs.118613

    Figure Lengend Snippet: Ac2-26 administration treats established nephritis in MRL/ lpr mice. (A) Ac2-26 treatment protocol for MRL/ lpr mice. Ac2-26 (2 mg/kg) or PBS treatments were administered i.p. every other day from weeks 10 to 20. n = 6 per group. (B) Levels of anti-dsDNA antibodies in different groups at 10 weeks and 20 weeks (n = 6). (C) Serum creatinine levels in different groups at 10 weeks and 20 weeks (n = 6). (D) Urinary protein/creatinine ratios in different groups at 10 weeks and 20 weeks (n = 6). (E) Representative sections of renal tissue stained with H&E, Masson's trichrome, PAS, and PASM staining and semi-quantitative evaluation of glomerulonephritis at 20 weeks. Bars = 50 μm. (F) Representative photomicrographs and quantitative analysis of Sirius Red staining at 20 weeks. n = 5 per group. Bars = 50 μm. (G) Immunohistochemical staining and quantitative analysis of F4/80 at 20 weeks. n = 5 per group. Bars = 50 μm. (H) Immunohistochemical staining and quantitative analysis of osteopontin (encoded by Spp1 ) at 20 weeks. n = 5 per group. Bars = 50 μm. (I) Representative photomicrographs and quantitative analysis of Oil Red O staining at 20 weeks. n = 5 per group. Bars = 50 μm. (J) Immunohistochemical staining and quantitative analysis of Fabp4 at 20 weeks. n = 5 per group. Bars = 50 μm. Data analyses were performed by Student's t -test for two groups. * P < 0.05; ** P < 0.01; *** P < 0.001. i.p.: intraperitoneally; HE: hematoxylin-eosin; PAS: periodic acid-Schiff; PASM: periodic acid-silver methenamine.

    Article Snippet: The Ac2-26 peptide was synthesized by MedChemExpress LLC (China), and the purity of Ac2-26 was 99.14%.

    Techniques: Staining, Immunohistochemical staining

    Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed to recombinant human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test

    Journal: Molecular Cancer

    Article Title: Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms

    doi: 10.1186/s12943-026-02611-y

    Figure Lengend Snippet: Patient-derived PanNET tumoroids express HH signaling proteins and respond to HH pathway activation and inhibition. A Combined fluorescence and phase-contrast images of 21-day-old human PanNET tumoroids (PanNET3) stained for chromogranin A (CHGA) and HH proteins (PTCH1, SHH). B Four patient-derived PanNET tumoroid lines (PanNET1–4) were exposed to recombinant human SHH N-terminal peptide (100 ng/mL) or the SMO inhibitor vismodegib (VISMO, 20 µM) for 72 h and changes in mRNA expression were analyzed by RT-qPCR. mRNA changes were normalized to HPRT1 expression and DMSO vehicle control. ( n = 4 unique patient lines). * = p < 0.05, ** = p < 0.01, **** = p < 0.0001 by Two-way ANOVA with Sidak post-test. C EdU labeling showing proliferation of dissociated PanNET3 cells following 5-day exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). D Quantitation of the percentage of EdU-positive PanNET tumor cells following 5-day treatment. ( n = 3 replicates from one patient tumoroid line). * = p < 0.05, by One-way ANOVA with Tukey post-test. E SHH or SAG were co-administered with the respective pharmacologic inhibitors and EdU uptake was evaluated after 7 days. F Immunofluorescent images of CHGA, SHH, and PTCH1 expression in a second PanNET tumoroid line (PanNET5). G , H EdU labeling was evaluated in PanNET5 tumoroids following 7-day treatment with SHH-N (200 ng/mL) and SAG (20 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 5 µM). I Crystal violet staining of human BON-1 PanNET cells after 48 h treatment. J BrdU incorporation in BON-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. M Immunofluorescent images of CHGA, SHH, and PTCH1 expression in tumoroids derived from a metastatic ileal NET (IL-NET-met1). N , O EdU labeling was assayed in the IL-NET-met1 tumoroid line following 7-day treatment with the same drug concentrations used for PanNET5. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test

    Article Snippet: Drug compounds used in the studies include: human recombinant SHH N-terminal peptide (R&D Systems, Cat# 1845-GMP), SAG (Tocris, Cat# 4366), vismodegib (Tocris, Cat# 7710), sonidegib (Tocris, Cat# 7826), GANT61 (Tocris, Cat# 3191), and itraconazole (Tocris, Cat# 5981).

    Techniques: Derivative Assay, Activation Assay, Inhibition, Fluorescence, Staining, Recombinant, Expressing, Quantitative RT-PCR, Control, Labeling, Quantitation Assay, BrdU Incorporation Assay

    HH signaling regulates the growth of GFAP ΔMen1 and Sox10 ΔMen1 pancreatic NET tumoroids. A Phase contrast and ( B ) fluorescence images of PanNET tumoroids from Sox10-Cre; Men1 FL/FL ; LSL-tdTomato mice. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure PanNET tumoroid growth in the presence of HH pathway agonists or ( D ) inhibitors of the canonical and ( E ) non-canonical HH signaling pathways. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates in two unique mouse PanNET tumoroid lines). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F BrdU incorporation was used to measure tumoroid proliferation in GFAP ΔMen1 and Sox10 ΔMen1 PanNET tumoroids after 72 h treatment. ( n = 4). ** = p < 0.01, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. G Relative fold-change in Chga mRNA levels in PanNET tumoroids following 72 h treatment. ( n = 5). H Western blot analysis of HH pathway proteins in PanNET tumoroids after 72 h treatment. I Quantitation of SHH protein expression normalized to beta-actin and DMSO vehicle control from the western blot analysis in panel ( H ). ( n = 3). J Western blot analysis and ( K ) associated quantitation of phosphorylated and total ERK and AKT growth pathways in PanNET tumoroids after 72 h treatment. ( n = 3). * = p < 0.05, ** = p < 0.01, *** = p < 0.001 by Kruskal-Wallis test

    Journal: Molecular Cancer

    Article Title: Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms

    doi: 10.1186/s12943-026-02611-y

    Figure Lengend Snippet: HH signaling regulates the growth of GFAP ΔMen1 and Sox10 ΔMen1 pancreatic NET tumoroids. A Phase contrast and ( B ) fluorescence images of PanNET tumoroids from Sox10-Cre; Men1 FL/FL ; LSL-tdTomato mice. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure PanNET tumoroid growth in the presence of HH pathway agonists or ( D ) inhibitors of the canonical and ( E ) non-canonical HH signaling pathways. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates in two unique mouse PanNET tumoroid lines). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F BrdU incorporation was used to measure tumoroid proliferation in GFAP ΔMen1 and Sox10 ΔMen1 PanNET tumoroids after 72 h treatment. ( n = 4). ** = p < 0.01, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. G Relative fold-change in Chga mRNA levels in PanNET tumoroids following 72 h treatment. ( n = 5). H Western blot analysis of HH pathway proteins in PanNET tumoroids after 72 h treatment. I Quantitation of SHH protein expression normalized to beta-actin and DMSO vehicle control from the western blot analysis in panel ( H ). ( n = 3). J Western blot analysis and ( K ) associated quantitation of phosphorylated and total ERK and AKT growth pathways in PanNET tumoroids after 72 h treatment. ( n = 3). * = p < 0.05, ** = p < 0.01, *** = p < 0.001 by Kruskal-Wallis test

    Article Snippet: Drug compounds used in the studies include: human recombinant SHH N-terminal peptide (R&D Systems, Cat# 1845-GMP), SAG (Tocris, Cat# 4366), vismodegib (Tocris, Cat# 7710), sonidegib (Tocris, Cat# 7826), GANT61 (Tocris, Cat# 3191), and itraconazole (Tocris, Cat# 5981).

    Techniques: Fluorescence, Protein-Protein interactions, Control, BrdU Incorporation Assay, Western Blot, Quantitation Assay, Expressing

    GFAP ΔMen1 DNETs and jejunal NETs are sensitive to HH pathway activation and inhibition. A Phase contrast and ( B ) fluorescence images of DNET tumoroids from a GFAP-Cre; Men1 FL/FL ; LSL-tdTomato mouse. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure DNET tumoroid growth in the presence of HH pathway inhibitors. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates using one mouse DNET tumoroid line). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. D Relative BrdU incorporation in a second GFAP ΔMen1 DNET tumoroid line and ( E ) a jejunal tumoroid line (J-NET) after 72 h treatment. ( n = 4). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F Western blot analysis of SHH, ERK, and AKT growth pathways in J-NET tumoroids after 72 h treatment. G Western blot quantitation of SHH and ( H ) phosphorylated and total ERK and AKT proteins normalized to GAPDH and DMSO vehicle control. ( n = 3). * = p < 0.05 by Kruskal-Wallis test. I Crystal violet staining of mouse STC-1 SI-NET cells after 48 h treatment with agonists and inhibitors of the HH signaling pathway. J BrdU incorporation in STC-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test

    Journal: Molecular Cancer

    Article Title: Hedgehog signaling drives glial cell plasticity and oncogenic reprogramming in gastroenteropancreatic neuroendocrine neoplasms

    doi: 10.1186/s12943-026-02611-y

    Figure Lengend Snippet: GFAP ΔMen1 DNETs and jejunal NETs are sensitive to HH pathway activation and inhibition. A Phase contrast and ( B ) fluorescence images of DNET tumoroids from a GFAP-Cre; Men1 FL/FL ; LSL-tdTomato mouse. Tumoroids were imaged after 72 h exposure to: the HH agonists SHH-N (100 ng/mL) and SAG (10 nM); inhibitors of the canonical HH signaling pathway vismodegib (20 µM) and sonidegib (10 nM); or inhibitors of the GLI1/2 effectors GANT61 (10 µM) and itraconazole (ITZ, 1 µM). C TdTomato fluorescence intensity was used to measure DNET tumoroid growth in the presence of HH pathway inhibitors. Fluorescence signal is compared to DMSO vehicle control. ( n = 3 replicates using one mouse DNET tumoroid line). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. D Relative BrdU incorporation in a second GFAP ΔMen1 DNET tumoroid line and ( E ) a jejunal tumoroid line (J-NET) after 72 h treatment. ( n = 4). ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test. F Western blot analysis of SHH, ERK, and AKT growth pathways in J-NET tumoroids after 72 h treatment. G Western blot quantitation of SHH and ( H ) phosphorylated and total ERK and AKT proteins normalized to GAPDH and DMSO vehicle control. ( n = 3). * = p < 0.05 by Kruskal-Wallis test. I Crystal violet staining of mouse STC-1 SI-NET cells after 48 h treatment with agonists and inhibitors of the HH signaling pathway. J BrdU incorporation in STC-1 cells after 48 h treatment with HH agonists SHH-N and SAG, ( K ) SMO inhibitors vismodegib and sonidegib, and ( L ) inhibitors of GLI1/2 signaling. * = p < 0.05, ** = p < 0.01, *** = p < 0.001, **** = p < 0.0001 by One-way ANOVA with Dunnett post-test

    Article Snippet: Drug compounds used in the studies include: human recombinant SHH N-terminal peptide (R&D Systems, Cat# 1845-GMP), SAG (Tocris, Cat# 4366), vismodegib (Tocris, Cat# 7710), sonidegib (Tocris, Cat# 7826), GANT61 (Tocris, Cat# 3191), and itraconazole (Tocris, Cat# 5981).

    Techniques: Activation Assay, Inhibition, Fluorescence, Control, BrdU Incorporation Assay, Western Blot, Quantitation Assay, Staining