Effect of metformin on cell proliferation, apoptosis, migration and invasion in A172 glioma cells and its mechanisms.

The purpose of the present study was to determine the effects of metformin on the inhibition of proliferation, apoptosis, invasion and migration of A172 human glioma cells in vitro and determine the underlying mechanism. The effects of metformin at different concentrations (0, 0.1, 1 and 10 mmol/l) on the inhibition of A172 cell proliferation were detected using a 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide assay. Cell apoptosis was detected by flow cytometry. Caspase­3 activity was analyzed by spectrophotometry. The invasion and migration of cells were detected by Transwell assays. The levels of Bcl­2­associated X protein (Bax), B­cell lymphoma 2 (Bcl­2), AMP­activated protein kinase (AMPK), phosphorylated­(p)AMPK and mechanistic target of rapamycin (mTOR) protein expression were detected by western blot analysis, and changes in the malondialdehyde (MDA) content and activity of superoxide dismutase (SOD) were determined. Compared with the control group, metformin significantly increased the inhibition of proliferation and apoptosis, and significantly reduced the invasion and migration of A172 cells in dose­ and time­dependent manners (P<0.05). In addition, compared with the control group, metformin significantly enhanced the activity of caspase­3, increased the expression of AMPK/pAMPK/Bax proteins and reduced the expression of mTOR/Bcl­2 proteins (P<0.05). Metformin increased the MDA content and reduced the activity of SOD in a dose­dependent manner (P<0.05). Metformin may inhibit glioma cell proliferation, migration and invasion, and promote its apoptosis; the effects may be associated with the AMPK/mTOR signaling pathway and oxidative stress.