Glycolysis And Its Inhibitors Effect On Ovarian Cancer Cell Growth And Proliferation In Vitro

Objective: Recent epidemiologic evidence suggests that obesity may alter the pathogenesis of ovarian cancer.Cancer cell metabolism is required to support the biosynthetic demands of cell growth and cell division,and to maintain reduction oxidation(redox)homeostasis.This study was designed to test the effects of glucose and glutamine on ovarian cancer cell growth,through the possible relationship between glycolysis and glutaminolysis.SKOV3,IGROV-1 and Hey cells were assayed for glucose,glutamine and the inhibitors dependence by analyzing cytotoxicity,cell cycle progression,apoptosis and ATP production.Methods: All The effect of glucose and glutamine on ovarian cancer cell growth lines was assessed by MTT assay,cell cycle analysis,annexin V assay,caspase 3 assay and flow cytometry.ATP level was assessed by a Luminometric ATP Assay Kit.Lactate production was measured by a L-Lactate Assay Kit.P-AMPK,P-S6,CDK4,P21,cyclinD1,Mcl-1,Bcl-2 and other proteins were detected by Western immunoblotting.Results: Glucose and glutamine are two major nutrients essential for cell proliferation in ovarian cancer cells.Glucose promoted cell proliferation and increased ATP and lactate production in all three cell lines.The combination of glucose,glutamine and pyruvate caused the maximal cell proliferation.Depletion of glucose induces apoptosis in ovarian cancer cells.Glucose also affects cell cycle progression in ovarian cancer cells.The 2-DG,3-BP and AOA inhibited cell growth in ovarian cancer cells.AOA increased sensitivity to 2-DG in inhibition of cell proliferation.AOA synergistically enhances the antiproliferative effect of 2-DG on ovarian cancer cells.Conclusions: Glucose represents the most important source of energy for ovarian cancer cells.The combined use of glycolytic inhibitors and AOA may have a new therapeutic application for ovarian cancer,which warrants additional investigation and should be explored in future research.