Farnesoid X receptor suppresses pancreatic cancer cell proliferation through negative regulation of matrix metalloproteinase 7

Objective To investigate the correlation between the expression of farnesoid X receptor (FXR) and matrix metalloproteinase 7 (MMP7) in pancreatic cancer cells, and to elucidate the role of FXR in regulating pancreatic cancer cell proliferation. Methods The effects of FXR on proliferation and MMP7 expression in pancreatic cancer cells (BxPC-3, PANC-1) were evaluated by in vitro experiments (CCK-8 assay, RT-PCR and Western blot). Bioinformatics analysis using GEPIA2 was performed to assess FXR/MMP7 expression and clinical prognosis in pancreatic cancer tissues, with immunohistochemistry (IHC) validating their correlation. Results FXR activation by GW4064 significantly inhibited pancreatic cancer cell proliferation (P＜0.05) and down-regulated MMP7 mRNA and protein levels (P＜0.01); while FXR inhibition by NDB significantly increased pancreatic cancer cell proliferation (P＜0.01) and upregulated the expression of MMP7 mRNA and protein(P＜0.001,P＜0.01). Bioinformatics analysis indicated that MMP7 was highly expressed in pancreatic adenocarcinoma tissues (P＜0.05), and its high expression was significantly associated with poor patient prognosis (P＜0.05); while no statistically significant association was found between FXR and prognosis. IHC (n=16) suggested an inverse correlation between FXR and MMP7 expression (R2=0.536 9). Conclusions FXR suppresses pancreatic cancer cell proliferation by negatively regulating MMP7, suggesting the BA(bile acid)-FXR-MMP7 axis as a potential therapeutic target.