Fig. 1.

Metformin sensitized hypoxic tumor cells to sorafenib. a Hypoxic tumor cells were resistant to sorafenib compared to cells under normoxia. MHCC97H cells were treated with 400 μM CoCl₂ for 24 h, then incubated with sorafenib or metformin for another 48 h. Cell viability, assessed by the CCK8 method, was expressed as the percent of control for different concentrations. Western blot was used to evaluate the effect of metformin and sorafenib alone or combined on HIF-2α. b Under CoCl₂ (400 μM) treatment, metformin had slight effect on HIF-2α protein expression, but sorafenib promoted HIF-2α protein expression. c Combined treatment of metformin and sorafenib noticeably minimized the expression of HIF-2α under CoCl₂ (400 μM) treatment