Abstract A54: Evaluation of effect of metformin and its various combinations on epithelial ovarian cancer

Abstract

Abstract Background & objectives: Ovarian cancer is the third most common cause of cancer in Indian women, the most common being epithelial type. Most patients relapse within 1-2 years of treatment and develop resistance to chemotherapy. The identification of new drugs with ability to resensitise ovarian cancer cells to existing chemotherapy has become a major challenge. In this study we have attempted to evaluate the effect of metformin (an antidiabetic drug) in ovarian cancer as it has shown promising effects in other solid tumours. Methods: Primary culture of ovarian cancer cells was established from ascitic fluid of untreated ovarian cancer patients. The cells were treated with carboplatin, paclitaxel and metformin alone and their various combinations and their ability to induce apoptosis seen. In vitro drug dosage was established using the MTT assay. The control and treated cells were then analysed by flowcytometry. Results: The mean percentage apoptosis in untreated control cells was 4.9 %( range from4-8%), with metformin for 48 hrs was 12.7 %( 9-16.8%), carboplatin 14.2% (9.9-20%), paclitaxel 16.06% (10-20.5%) , metformin and carboplatin 20.2% (12-28.4%), metformin and paclitaxel 26% (18.2-29%), carboplatin and paclitaxel 22.2% (16-27.3%), metformin carboplatin, paclitaxel combination 49% (46-55%)i.e. maximum. Interpretation & conclusions: Metformin treatment significantly inhibited the proliferation of primary ovarian cancer cells culture. At the cellular level, metformin interferes with cell cycle leading to G0/G1 or S phase arrest. Besides its anti-neoplastic activity as a single agent, metformin treatment with carboplatin and paclitaxel demonstrated increase apoptosis as compared to single agents alone offering its potential as a therapeutic agent with carboplatin and paclitaxel for epithelial ovarian cancer. Citation Format: Seema Patel, Neeta Singh. Evaluation of effect of metformin and its various combinations on epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A54.