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.

Key words: pancreatic cancer, metformin, glucose, microRNA, miR-139-5p