The clinical use of doxorubicin (DOX) is limited due to its systemic side effects and drug resistance. Recent evidence suggests that metformin prevents and controls certain but not all types of cancer. The beneficial use of metformin in combination with some chemotherapeutic agents has been reported. The aim of this study is to investigate the influence of metformin on DOX-induced effects in human prostate DU145 cancer cells and clarify its molecular mechanisms. For this purpose, DU145cells were treated with DOX or metformin, either alone or in combination with each other. The proliferation of DU145cells was inhibited by DOX-alone and metformin-alone treatment inatimeanddose-dependentmanner.MetformincouldenhancethecytotoxicityofDOXbyincreasing DOX cellular uptake and cell cycle arrest at G1/S checkpoint which is associated with the enhancement of p21 protein expression. Moreover, metformin could elevate DOX-induced apoptosis in DU145cells in a concentration-dependentmannerandDOX-inducedcaspase-3activity.These findingssuggestthatthecombinedtreatment of metformin with DOX potentiates the anticancer efficacy of DOX inDU145cells via inhibiting ABCB1 function, cell cycle arrest at G1/S transition and apoptosis induction.

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