Metformin inhibits ovarian cancer growth and increases sensitivity to paclitaxel in mouse models

netic mouse model of ovarian cancer was used. Mice were treated with placebo, paclitaxel (3 mg/kg/wk intraperitoneally for 7 weeks), metformin (100 mg/kg/d in water for 7 weeks), or paclitaxel plus metformin, and tumor volume was compared among treatment groups. RESULTS:Invitro,metformindecreasedproliferationofovariancancer cell lines and induced cell cycle arrest, but not apoptosis. Further analysis showed that metformin altered several aspects of metabolism including adenosine monophosphateeactivated protein kinase activity, glycolysis, and lipid synthesis. In the prevention mouse model, mice that were pretreated with metformin had 60% fewer tumor implantscomparedwithcontrols(P<.005).Inthetreatmentstudy,mice that were treated with paclitaxel plus metformin had a 60% reduction in tumor weight compared with controls (P ¼ .02), which is a level of tumor reduction greater than that resulting from either paclitaxel or metformin alone. CONCLUSION: Based on these results, we conclude that metformin alters metabolism in ovarian cancer cells, prevents tumor growth, and increases sensitivity to chemotherapy in vitro and in mouse models. These preclinical findings suggest that metformin warrants further investigation for use as an ovarian cancer therapeutic.