Metformin improves the therapeutic effect of metronomic cyclophosphamide in breast cancer animal model

Abstract

Background:Metronomic chemotherapy (MCT) refers to chronic low doses administration of chemotherapeutic agents without prolonged rest periods which mainly causes antiangiogenic activity and immunomodulatory effects. In this study, we tried to investigate the synergistic action of metformin (MET) with metronomic cyclophosphamide (MTm CTX) in a breast cancer animal model.Materials and methods:A total of 50 female Swiss albino mice were S.C. injected in the right thigh by 2.5 × 106 of viable Ehrlich carcinoma cells and when the tumor reached ∼500 mm3, they are divided equally to five groups, one is untreated ESC control group, and the other treatment groups are high dose of cyclophosphamide (100 mg/kg body weight i.p. twice/week), metformin in drinking water (5mg/ml), low dose cyclophosphamide in drinking water (20 mg/kg body weight per day), and combination of low dose cyclophosphamide and metformin.Results: We found that MTm Cyclophosphamide with metformin was more effective than each monotherapy in reduction of angiogenesis, inflammation. In addition, we found that MTm CTX plus MET combined therapy treated group demonstrated a remarkable DNA damage in cancer cells close to the high dose cyclophosphamide treated group.Conclusion:The therapeutic benefits of combined MTm cyclophosphamide and MET on mammary adenocarcinoma animal model with low toxic profile may suggest a new effective treatment modality for some breast cancer patients.