cc 90009  (MedChemExpress)

Journal: Breast Cancer Research : BCR

Article Title: Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer

doi: 10.1186/s13058-025-02131-5

Figure Lengend Snippet: Tadalafil inhibits the immunosuppressive microenvironment in breast cancer. A Timeline schematic of the experimental paradigm. The treatment of PyMT mice was initiated at postnatal week 4, with daily intragastric gavage of tadalafil continuing until the mice reached 7 or 12 weeks of age. B Representative images of H&E staining of mouse mammary hyperplasia tissue. C Carmine-stained mouse mammary pads (mammary hyperplasia) represent the total area of the whole mammary hyperplasia lesion calculated from the image and ImageJ (LN: lymph nodes). D Representative dot plots of breast hyperplasia-infiltrated T cells, gated from CD45 + . E Representative dot plots of breast hyperplasia-infiltrated MDSCs, gated from CD11b + . F Representative images of tumor-bearing mice. G Tumor growth curve. H Number of mammary tumors in mice. I Representative images of tumor sections stained with H&E (black arrows indicate areas of tumor infiltration and red arrows indicate acinus). J Gating strategy to analyze immune cell populations in TME. K The proportion of T cells, tumor-associated macrophages, and MDSCs and the mean fluorescence intensity of PD-1 on CD8 + T cells were analyzed by flow cytometry. Data represents the mean ± SD ( n = 4–6), * P < 0.05, ** P < 0.01 versus vehicle, ns = no significant difference

Article Snippet: Tadalafil (HY-90009 A), STAT3 inhibitor (Tyrphostin AG490, HY-12000) and PARP-1 inhibitor (AG14361, HY-12032) were purchased from MedChem Express (New Jersey, USA).

Techniques: Staining, Fluorescence, Flow Cytometry

Journal: Breast Cancer Research : BCR

Article Title: Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer

doi: 10.1186/s13058-025-02131-5

Figure Lengend Snippet: Tadalafil reduces lung metastasis of breast cancer by inhibiting MDSCs invasion. A Timeline schematic of the experimental paradigm. The treatment of PyMT mice was initiated at postnatal week 6, with daily intragastric gavage of tadalafil continuing until the mice reached 14 weeks of age. B Tumor growth curve. C Representative H&E staining images of mouse lung tissues (metastatic nodules indicated by black arrows) and the number of metastatic nodules counted. D Representative dot plots and proportion of MDSCs. E Representative dot plots and proportion of T cells. F The levels of IL-10, CCL2, IFN-γ and IL-12 in primary tumor supernatant were measured. G Experimental protocol for mouse postoperative metastasis model. The next day after tumor resection, mice initiated treatment with tadalafil via intragastric gavage daily for 4 weeks. H Luciferase imaging of the lung metastasis model of BALB/c breast cancer after operation. I Representative map of lung metastases in mice detected by H&E staining (arrows indicate metastatic nodules) and S100A8 + myeloid cells in the lung by immunohistochemical staining (For each slice, three fields of view are randomly selected to calculate the percentage of positive results. Each dot represents one field of view). J Statistical plot of fluorescence quantum analysis of mouse tumor metastases using Caliper Life Sciences software. K The number of pulmonary metastatic nodules was counted. L Scatter plot of the positive rate of S100A8 + myeloid cells quantified in the lung. M Gating strategy and proportion of MDSCs by flow cytometry. Data represents the mean ± SD ( n ≥ 5), * P < 0.05, ** P < 0.01 and ** P < 0.001 versus vehicle, ns = no significant difference

Article Snippet: Tadalafil (HY-90009 A), STAT3 inhibitor (Tyrphostin AG490, HY-12000) and PARP-1 inhibitor (AG14361, HY-12032) were purchased from MedChem Express (New Jersey, USA).

Techniques: Staining, Luciferase, Imaging, Immunohistochemical staining, Fluorescence, Software, Flow Cytometry

Journal: Breast Cancer Research : BCR

Article Title: Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer

doi: 10.1186/s13058-025-02131-5

Figure Lengend Snippet: Tadalafil disrupted the differentiation and immunosuppressive function of MDSCs. A Schematic representation of the in vitro induced differentiation of bone marrow cells into MDSCs. B Gating strategy and Gr-1 proportion by flow cytometry. C , D Representative Western blot images ( C ) and quantitative analysis ( D ) of iNOS, arginase 1 and CCL2 protein expression levels in Cytokines induced MDSCs after tadalafil intervention. E , F Representative Western blot images ( E ) and quantitative analysis ( F ) of iNOS, arginase 1 and CCL2 protein expression levels in 4T1 CM-induced MDSCs after tadalafil intervention. G Representative contour plots and proportions of Arginase 1. H Flow cytometry gating strategy and CD8 + T proliferation rate analysis. I Histograms and quantification show that MDSCs were co-cultured 72 h with anti-CD3/anti-CD28 monoclonal antibody stimulated T cells (CFSE labeled) at a ratio of 1:2 T cells to MDSCs. J Representative images and quantification of crystal violet staining in transwell chambers; Scale bar: 100 μm. Data represents the mean ± SD ( n = 3), *P < 0.05, **P < 0.01 and **P < 0.001 versus vehicle, ns = no significant difference

Article Snippet: Tadalafil (HY-90009 A), STAT3 inhibitor (Tyrphostin AG490, HY-12000) and PARP-1 inhibitor (AG14361, HY-12032) were purchased from MedChem Express (New Jersey, USA).

Techniques: In Vitro, Flow Cytometry, Western Blot, Expressing, Cell Culture, Labeling, Staining

Journal: Breast Cancer Research : BCR

Article Title: Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer

doi: 10.1186/s13058-025-02131-5

Figure Lengend Snippet: Tadalafil significantly inhibited the expression of chemokines associated with MDSCs and inhibited the remodeling process of ECM. A The volcano plot showing the differentially expressed genes in MDSCs generated by cytokine induction between the tadalafil intervention group and the non-intervention group. B GO analysis of targets of tadalafil treatment (green for Biological Process, orange for Cellular Component, and blue for Molecular Function). C KEGG pathway enrichment analysis of differential genes. D Gene enrichment analysis showing the characteristics of genes involved in monocyte chemotaxis, NES, normalized enrichment score. E Heat map of the relative expression of monocyte chemoattraction-related genes in the control and tadalafil treatment groups. F Chemokine mRNA expression levels. G , H Representative Western blot images ( G ) and quantification ( H ) of Fibronectin, Laminin, E-cadherin, and mmp2 proteins. Data represents the mean ± SD ( n ≥ 3), *P < 0.05, **P < 0.01 and **P < 0.001 vs. vehicle or control

Article Snippet: Tadalafil (HY-90009 A), STAT3 inhibitor (Tyrphostin AG490, HY-12000) and PARP-1 inhibitor (AG14361, HY-12032) were purchased from MedChem Express (New Jersey, USA).

Techniques: Expressing, Generated, Chemotaxis Assay, Control, Western Blot

Journal: Breast Cancer Research : BCR

Article Title: Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer

doi: 10.1186/s13058-025-02131-5

Figure Lengend Snippet: Tadalafil disrupted the immunosuppressive ability of MDSCs by inhibiting STAT3 transcription. A RT-qPCR analysis of the expression of the BM-MDSCs stat3 . B Western blot analysis was used to detect STAT3 expression in BM-MDSCs after tadalafil treatment. C Flow cytometry representative plot of the effect of tadalafil treatment combined with administration of the STAT3 inhibitor on the expression of arginase 1, a functional marker of MDSCs, induced in vitro. D Transwell co-culture plate design. E Representative images and quantification of heme staining in transwell chambers. Data represents the mean ± SD ( n ≥ 3), **P < 0.01 and **P < 0.001 versus vehicle

Article Snippet: Tadalafil (HY-90009 A), STAT3 inhibitor (Tyrphostin AG490, HY-12000) and PARP-1 inhibitor (AG14361, HY-12032) were purchased from MedChem Express (New Jersey, USA).

Techniques: Quantitative RT-PCR, Expressing, Western Blot, Flow Cytometry, Functional Assay, Marker, In Vitro, Co-Culture Assay, Staining

Journal: Breast Cancer Research : BCR

Article Title: Modulating phosphodiesterase-5 activity to suppress the immunosuppressive mechanisms of myeloid-derived suppressor cells in breast cancer

doi: 10.1186/s13058-025-02131-5

Figure Lengend Snippet: Tadalafil regulates STAT3 transcription through PARP1. A GSEA analysis revealed significant alterations in NAD-related signaling pathways following tadalafil intervention in BM-MDSCs. B Heatmap displaying the expression patterns of genes associated with NAD-related signaling pathways. C Flow cytometry gating strategy and analysis of PARP1 median fluorescence intensity in BM-MDSCs. D Western blot analysis of cGKI and PARP1 expression in MDSC cells after tadalafil treatment. E The expression level of PARP1 mRNA in BM-MDSCs. F Immunofluorescence staining assessing PARP1 expression in BM-MDSCs post-tadalafil treatment. G Western blot detection of PARP1, STAT3, and phosphorylated STAT3 (p-STAT3) levels in cytoplasmic and nuclear fractions of BM-MDSCs upon tadalafil intervention. H Western blot analysis of STAT3 and p-STAT3 expression changes in BM-MDSCs treated with tadalafil in the presence of a PARP1 inhibitor. I Flow cytometry gating strategy and analysis of p-STAT3 median fluorescence intensity in BM-MDSCs. J Genotyping verification of PARP1 knockout mice. K Western blot confirmation of PARP1 knockout efficiency. L Western blot evaluation of Arg1, STAT3, and p-STAT3 expression in BM-MDSCs from PARP1 knockout mice following tadalafil intervention. Data represents the mean ± SD ( n ≥ 3), *P < 0.05, **P < 0.01 and **P < 0.001 vs. vehicle

Article Snippet: Tadalafil (HY-90009 A), STAT3 inhibitor (Tyrphostin AG490, HY-12000) and PARP-1 inhibitor (AG14361, HY-12032) were purchased from MedChem Express (New Jersey, USA).

Techniques: Protein-Protein interactions, Expressing, Flow Cytometry, Fluorescence, Western Blot, Immunofluorescence, Staining, Knock-Out