lif receptor lifr inhibitor  (MedChemExpress)

Journal: bioRxiv

Article Title: Targeting CREB remodels the immune microenvironment to enhance immunotherapy responses in pancreatic cancer

doi: 10.64898/2025.12.04.691935

Figure Lengend Snippet: Cancer cell intrinsic CREB transcriptionally regulates LIF expression, driving macrophage-modulatory signaling in PDAC. (A) Experimental schematic demonstrating RNA sequencing (RNA-seq) analysis conducted in KPC mouse CREB WT and CREB KO tumor cells. (B) Bubble plot visualizing differentially regulated pathways (using molecular signature databases) in CREB KO transcriptomics compared with CREB WT tumor cells (n=3). (C) Ridge plot showing normalized enrichment scores for the hallmark JAK–STAT3 signaling pathway across different cellular constituents in the human HTAN pancreatic cancer dataset from treatment-naïve patients. (D) Western blot image depicting pSTAT3 activation, along with tSTAT3, vinculin and vimentin in mouse RAW macrophage 264.7 cell line treated with either recombinant (r) LIF alone (1 µg/mL) or in combination with EC359 (LIFR blockade, 0.2µM). (E) Chromatin Immunoprecipitation sequencing (ChIP-seq) peak signals visualized as heat maps which depict CREB binding sites across genomic regions in KPC mouse pancreatic tumor cells. The adjacent call out boxes with the heat maps showing essential genes regulated via CREB as its downstream mediators. (F) Integrative Genome Viewer (IGV) plot visualizing occupancy of CREB binding peaks in ChIP-seq data at the site of mouse Lif promoter gene regulatory sequences. (G-H) Violin dot plots showing downregulation of LIF expression via qPCR and ELISA in bulk tumor lysates of CREB KO KPC orthotopic PDAC tumors as compared to CREB WT with n=3-7 mice per group. (I) Representative photomicrographs of whole pancreas along with its corresponding quantification depicting significantly reduced LIF expression via IHC in age matched KPC C -/- as compared to KPC mice. Individual data points with mean ± SEM are shown and compared by two-tailed unpaired t test. *p<0.05; **p<0.01; ns non-significant (p>0.05).

Article Snippet: Under specific experimental conditions, bone marrow derived macrophages (BMDMs) were treated with murine recombinant LIF (Biotechne, 1 μg/mL), with or without pretreatment using an LIF receptor (LIFR) inhibitor (0.2 μM EC359, HY-120142, MedChem Express) at 37°C for 30 minutes.

Techniques: Expressing, RNA Sequencing, Western Blot, Activation Assay, Recombinant, ChIP-sequencing, Binding Assay, Enzyme-linked Immunosorbent Assay, Two Tailed Test

Journal: Cancer Medicine

Article Title: CTHRC 1 Derived From Cancer‐Associated Fibroblasts Promotes Pancreatic Cancer Progression and Metastasis via the LIF ‐ STAT 3 Pathway

doi: 10.1002/cam4.71126

Figure Lengend Snippet: CTHRC1 in CAFs mediates the activation of STAT3 signaling pathway in pancreatic cancer cells by positively regulating LIF. (A) Western Blot was used to detect the activation of STAT3 signaling pathway in Panc‐1 after adding EC330 in CAFs‐CM and protein gray scale analysis. (B) Western Blot was used to detect the activation of STAT3 signaling pathway in Aspc‐1 after adding EC330 in CAFs‐CM and protein gray scale analysis. (C) Effect of CAFs‐CM on the proliferation function of Panc‐1 after adding EC330. (D) Effect of CAFs‐CM on the colony‐forming function of Panc‐1 after adding EC330. (E) Effect of CAFs‐CM on the migration function of Panc‐1 after adding EC330. (F, G) Western Blot was used to detect the activation of STAT3 signaling pathway in Panc‐1 after adding EC330 in CAFs‐CM overexpressing CTHRC1 and protein gray scale analysis. (H) Effect of CAFs‐CM overexpressing CTHRC1 on the proliferation function of Panc‐1 after adding EC330. (I, J) Effect of CAFs‐CM overexpressing CTHRC1 on the colony‐forming function of Panc‐1 after adding EC330. (K) Effect of CAFs‐CM overexpressing CTHRC1 on the migration function of Panc‐1 after adding EC330. (L) Effect of CAFs‐CM on the proliferative function of Aspc‐1 after adding Stattic. (M) Effect of CAFs‐CM overexpressing CTHRC1 on the migration function of Aspc‐1 after adding Stattic. ** p < 0.01; *** p < 0.001.

Article Snippet: LIF inhibitor EC330 was purchased from MedChemExpress (MCE).

Techniques: Activation Assay, Western Blot, Migration