Effect of metformin on apoptosis, cell cycle arrest migration and invasion of A498 cells.

Previous studies have demonstrated that metformin (Met) may reduce the risk of cancer development. In the present study, the anti-cancer effects of Met in A498 cells were investigated. It was found that Met inhibited A498 cell proliferation in a time- and dose-dependent manner, as well as induced the activation of AMP-activated protein kinase. It was also demonstrated that Met promoted A498 cell apoptosis and mechanistic studies suggested that this was mediated by the downregulation of B-cell lymphoma 2 and concurrent upregulation of Bcl-2-associated X protein. In addition, it was observed that Met induced G1 cell cycle arrest by decreasing cyclin D1 expression. Furthermore, the results demonstrated that Met reduced A498 cell migration and invasion in vitro by decreasing matrix metalloproteinase-2, which indicated its potential to inhibit renal cancer metastasis. In combina- tion, these results provide evidence that Met is important in anti-renal cancer therapy, and thus may serve as a novel and efficient agent for renal cancer treatment.