Fig. 5.

Metformin synergized with sorafenib to suppress angiogenesis, proliferation, and EMT but promote apoptosis in vivo. Representative images of tumor sections were stained with antibody against CD31, Ki67, and TUNEL (magnification ×200). a Metformin in combination with sorafenib synergistically minimized both Ki67 and CD31 expression but promoted TUNEL expression. b Combined therapy inhibited EMT at protein level which lysated from the tumor tissue, and pAMPK expression was elevated both in metformin group and combined treatment groups. c Combined treatment of metformin and sorafenib suppressed HIF-2α protein expression but upregulated TIP30 protein expression evaluated by Western blot