Effect and mechanism of metformin on TGF-β1expression in pancreatic cancer / 西安交通大学学报(医学版)

ABSTRACT

Objective: To investigate the effect of metformin on TGF-β1 expression in pancreatic cancer and further analyze the underlying mechanism. Methods: After metformin intervention, cell proliferation and invasion ability were detected by MTT assay and Transwell method, respectively. The expression of TGF-β1 in pancreatic cancer cell lines Panc-1 and BxPC-3 was detected by qRT-PCR, Western blot and immunofluorescence. The expression of AMPK/p-AMPK was detected by Western blot; ELISA method was used to measure the content of TGF-β1 in cell supernatant. After silencing AMPK expression in pancreatic cancer cell lines, the cells were treated with metformin and the expression of TGF-β1 was detected by qRT-PCR and Western blot. Results: The phosphorylation level of AMPK in Panc-1 (P<0.001) and BxPC-3 (P<0.001) cells was significantly decreased after metformin intervention. In addition, the expression of TGF-β1 in tumor cells was significantly decreased. However, the reduced expression of TGF-β1 by metformin was reversed by AMPK silencing in cancer cells (P<0.05). Conclusion: Metformin can inhibit TGF-β1 expression in pancreatic cancer cells by inducing AMPK phosphorylation.