Evaluation of Effects of Metformin in Primary Ovarian Cancer Cells


Background: Ovarian cancer is the third most common cause of cancer in Indian women. Despite an initial70-80% response rate, most patients relapse within 1-2 years and develop chemoresistance. Hence, identificationor repositioning of drugs to resensitise ovarian cancer cells to existing chemotherapy is needed. Traditionallyimmortalized cell lines have been used in research, but these may contain genetic aberrations and chromosomalabnormalities serving as poor indicators of normal cell phenotype and progression of early-stage disease. Theuse of primary cells, maintained for only short periods of time in vitro, may serve as the best representative forstudying in vivo conditions of the tissues from which they are derived. In this study we have attempted to evaluatethe effect of metformin (an antidiabetic drug) in primary ovarian cancer cells because of its promising effectin other solid tumours. Materials and
Methods: Primary cultures of epithelial ovarian cancer cells establishedfrom ascitic fluid of untreated ovarian cancer patients were used. The cells were treated with metformin at dosesstandardized by MTT assay and its ability to induce apoptosis was studied. The cells were analysed for apoptosisand apoptosis related proteins by flow cytometry and western blotting respectively.
Results: Metformin inducedapoptosis in ovarian cancer cells, provoking cell cycle arrest in the G0/G1 and S phase. It induced apoptosis inovarian cancer cells by, down-regulating Bcl-2 and up-regulating Bax expression.
Conclusions: Metformin wasable to induce apoptosis in primary ovarian cancer cells by modulating the expression of Bcl-2 family proteins.These data are relevant to ongoing translational research efforts exploring the chemotherapeutic potential ofmetformin.