Effect of metformin on growth of gastric cancer cells SGC7901 and BGC823 and action mechanism

Abstract

Objective To study the effect of metformin on the proliferation and apoptosis of gastric cancer cells SGC7901 and BGC823, and the possible mechanisms. Methods The effect of metformin on cell proliferation was determined using the cell counting kit-8 (CCK-8) assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. The effect of metformin on the expression of microRNA (miRNA, miR)-let-7a, Cyclin D1, cyclin-dependent kinase (Cdk)2, Cdk4 and p21 was detected by real-time quantitative polymerase chain reaction (Real-time PCR) and Western blotting. Results After treatment with different concentrations of metformin (0.5, 1.0, 2.0, 4.0, 8.0, 16.0, 32.0 mmol/L) for 72 h, the growth inhibitory rate of gastric cancer (GC) cell SGC7901 was (15.3±3.1)%, (24.7±6.8)%, (27.3±5.7)%, (31.0±9.6)%, (57.0±3.6)%, (69.0±2.0)% and (70.7±5.9)%, respectively(P=0.000). The growth inhibitory rate of GC cell BGC823 was (37.7±7.5)%, (44.7±2.1)%, (53.7±4.7)%, (59.3±6.4)%, (68.0±5.3)%, (75.7±2.5)% and (81.0±1.0)%, respectively (P=0.000). Metformin inhibited the proliferation of GC cells in a dose-time-dependent manner. The apoptosis rate of SGC7901 in metformin group and control group was (7.68±0.42)% and (2.63±0.72)% (P=0.000), and that of BGC823 in each group was (14.19±0.72)% and (11.31±1.29)% (P=0.028), respectively. Metformin arrested GC cell cycle in G1 phase. In the dosing group, the ratio of gastric cancer cells arresting at G1 phasewas significantly higher than that of the control group, [SGC7901: (57.3±0.6)% vs. (44.2±0.4)% , P=0.000; BGC823: (59.9±1.7)% vs. (52.6±1.7)% , P=0.007]. Metformin upregulated the expression of miR-let-7a, Cyclin D1, Cdk2 and Cdk4, and inhibited the expression of p21. Conclusion Metformin could inhibit the growth of SGC7901 and BGC823 gastric cancer cells by up-regulating the expression of miR-let-7a partly and regulate the cell cycle regulators to arrest the cell cycle progression and promote cell apoptosis. Key words: Metformin; Gastric cancer; MicroRNA; Cell cycle; Apoptosis