Figure 6.

Metformin inhibited tumor growth in the LKB1^fl/fl p53^fl/fl endometrial cancer mouse model. LKB1^fl/fl p53^fl/fl mice were fed high fat diet (HFD) or low fat diet (LFD) at 3 weeks of age to induce obesity. The mice were divided into four groups: obese, obese + metformin, lean and lean + metformin. HFD induced an increase in body weight in the LKB1^fl/fl p53^fl/fl mice (A). The levels of cholesterol were significantly increased in obese mice compared with lean mice (B). The obese and lean mice in both groups were treated with metformin (250 mg/kg, oral gavage) or placebo for 4 weeks. Obesity promoted tumor growth in obese mice versus lean mice. Metformin significantly reduced tumor weight in the obese and lean mice, with a great impact on tumor weight in obese mice (C and D). The changes of Ki-67, phosphorylated-S6, phosphorylated-AMPK, cyclin D and cleaved caspase 3 were assessed by immunohistochemistry in the endometrial cancer tissues. The expression of Ki-67, cyclin D and phosphorylated-S6 was significantly reduced and cleaved caspase 3 and phosphorylated-AMPK was increased in both groups after metformin treatment (E). *P < 0.05, **P < 0.01.