miR-139-5p enhances the inhibition effect of metformin on cell proliferation of pancreatic cancer cell line PANC-1 cultured in normal-glucose medium

Abstract

Objective To investigate the effects of metformin(Met) on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions, and to find the potential role of miR-139-5p in the process. Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L) in 25 mmol/L(high-glucose group,HG) or 5 mmol/L(normal-glucose group,NG) glucose culture, cell proliferation, apoptosis, migration and cell cycle were detected after 48 h. The expression of miR-139-5p was quantitatively detected by RT-qPCR, and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p. Results Metformin inhibited the proliferation, promoted apoptosis, and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions, and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups. The expression of miR-139-5p was up-regulated by metformin treatment in normal but not in high glucose culture. Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-proliferation effect of 5 mmol/L metformin. The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions. Conclusions In normal-glucose culture conditions, metformin can inhibit proliferation, induce apoptosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture, which may be partly related to the up-regulation of miR-139-5p.

Keywords

• pancreatic cancer|metformin|glucose|microrna|mir-139-5p