Metformin inhibits mTOR and c-Myc by decreasing YAP protein expression in OSCC cells

Abstract

Metformin is an antidiabetic drug that has been reported to have an inhibitory effect on different types of cancers, including oral squamous cell carcinoma (OSCC). However, few studies have explored the role of Yes-associated protein (YAP), a vital factor contributing to OSCC biology, in metformin-induced anticancer activity in OSCC cells. Thus, the purpose of the present study was to investigate the molecular relationship between metformin and YAP in OSCC cells. CAL27 and SCC25 cell lines were treated with various concentrations of metformin for 24 h. Cell proliferation was detected by Cell Counting Kit-8 (CCK-8) and flow cytometric assays. Cell apoptosis was analyzed using flow cytometry. The intracellular protein levels of target genes were determined by western blotting. It was demonstrated that metformin affected the cell cycle and apoptosis of CAL27 and SCC25 cells. Alteration of YAP protein expression affected metformin-mediated changes in the cell cycle and apoptosis of CAL27 and SCC25 cells. In addition, compared to the control treatment, metformin treatment decreased the protein levels of YAP, mTOR, p-mTOR and c-Myc. The overexpression of YAP alleviated the inhibitory effect of metformin on the protein expression of mTOR, p-mTOR and c-Myc. The combination of metformin and verteporfin markedly enhanced the effects of metformin on the protein expression of mTOR, p-mTOR and c-Myc. Therefore, the results of the present study suggest that metformin suppresses OSCC by inhibiting YAP protein expression and by suppressing the YAP-mediated effects of metformin on the protein expression of mTOR and c-Myc.