Metformin Inhibits Esophagus Cancer Proliferation through Upregulation of USP7

Abstract

BACKGROUND: Recent population studies suggest that the use of metformin is associated with reduced incidence and improved prognosis of certain cancers. METHODS: In the current study, we assessed the effect of metformin on esophagus cancer cells using two cell lines (Eca-109 and TE-1 cells). RESULTS: We found that metformin inhibited growth and decreased expression of cell-cycle regulators in these cells. Treatment with metformin was also associated with activation of AMP kinase and inhibition of mTOR/p70S6K/pS6 signaling in both cells. However, inhibition of AMPK signaling has little impact on the anti-proliferative roles of metformin. In addition, we found USP7, a positive regulator of tumor suppressor p53, as a new molecular target of metformin. Esophagus cancer cells can be protected against metformin-induced growth inhibition by small interfering RNA against USP7. CONCLUSION: These results provide evidence for a mechanism that may contribute to the antineoplastic effects of metformin suggested by recent population studies and justify further work to explore potential roles for it in esophagus cancer prevention and treatment.