Alteration of metabolic activities by modulation of PI3K/AKT and mTOR pathways in ovarian cancer cells (766.10)

Abstract

Ovarian cancer accounts for three percent of all cancers that affect women world‐wide and it is regarded at the deadliest form of gynecological cancer. Alteration in cellular metabolism is a manifestation of cancer that typically results in a shift from oxidative phosphorylation to aerobic glycolysis. This change is defined as the Warburg Effect. In this study, we used cell culture techniques to investigate the metabolic behavior of an ovarian cancer cell line, CaOV3. We determined metabolic activity through XF Cell Mito Stress and XF Glycolysis stress tests using a Seahorse Bioscience XFe96 Analyzer. After titrations were completed for optimal cell number and concentration of Oligomycin, we pretreated CaOV3 cells with PI3K/AKT and mTOR inhibitors and repeated stress tests. We found that under the influence of Rapamycin (mTOR inhibitor) and LY294002 (PI3K/AKT inhibitor), the cells exhibited an increase in oxygen consumption by OCR (pMoles/min) and ECAR (mpH/min) analysis, suggesting an increase in capacity for cellular respiration and subsequent ATP production. Our results also indicated that Doxarubicin, a commonly applied chemotherapy agent, does not affect metabolic levels. Taken together, we conclude that in response to the inhibition of the PI3K/AKT and mTOR pathway that promotes protein synthesis and proliferation, the cancer cells attempt to combat the effects by increasing their metabolic capacity. Our data also suggest that modulation of PI3K/AKT and mTOR pathways and alteration of metabolic activities may reveal molecular targets for ovarian cancer treatment.Grant Funding Source: Supported by INBRE