Inhibition of glycolysis enhances cisplatin-induced apoptosis in ovarian cancer cells

Abstract

Up-regulation of glycolysis has been demonstrated in multiple tumor types and is believed to originate as an adaptive response to the selective pressure of the tumor microenvironment. We hypothesized that ovarian cancer cells are dependent on the glycolytic pathway for adenosine triphosphate generation and that this phenotype could be exploited for therapeutic intervention. Expression of glucose transporter 1 (Glut1), phosphorylated protein kinase B (pPKB/pAkt), and phosphorylated mammalian target of rapamycin (pmTOR) was assessed in ovarian carcinoma tumors and cell lines. Cells were incubated with 2-deoxyglucose and rapamycin; growth inhibition, viability, and mechanism of cell death were determined. Ovarian carcinoma cells overexpress Glut1, pAkt, and pmTOR compared with benign ovarian epithelial cells. 2-deoxyglucose and rapamycin markedly enhance apoptotic and nonapoptotic cell death in ovarian cancer cells. The glycolytic phenotype of ovarian cancer cells can be targeted for therapeutic intervention. Combined treatment modalities that target multiple cellular pathways hold promise for the treatment of chemoresistant ovarian cancer cells.