Effect Of Albendazole On Survival And Chemoresistance By Inhibition Glycolysis Of Cisplatin-resistant Ovarian Cancer Cells

Objective： To investigate the effect of albendazole(ABZ) on thesurvival and chemoresistance of human cisplatin-resistant ovarian cancerSKOV3/DDP cells by inhibition glycolysis.Methods：The proliferation of SKOV3/DDP cells was detected bymethyl thiazolyl tetrazolium(MTT) colorimetry after treatment with ABZ invitro,then according to the inhibition concentrations of0%,25%,50%,75%to devide cells into4groups:control group,IC25group,IC50group,IC75group，in addition，devide every group into12h,24h and36h sub-groupsin accordance with ABZ’s action time.After treatment with ABZ, activitiesof hexokinase(HK) and pyruvate kinase(PK) were detected by colorimetry,activity of lactate dehydrogenase(LDH) was detected by ELIASA, theexpressions of Akt mRNA and Myc mRNA were detected by RT-PCR, thesurvival was investigated by acridine orange/ethidium bromide (AO/EB)double staining for fluorescence microscopy and flow cytometry(FCM),thecell cycles was detected by FCM, the P-gp expression was determined by flow cytometry at the setting points of time. The proliferation ofSKOV3/DDP cells was detected by methyl thiazolyl tetrazolium(MTT)colorimetry after treatment with ABZ combined and sequence withDDP,EPI or5-Fu.Results：After treatment with different concentrations of ABZ,theproliferation of SKOV3/DDP cells was inhibited by ABZ in vitro in adose-dependent manner,and the IC25was1.43±0.21μmol/L，IC50was8.64±0.74μmol/L,IC75was52.48±3.99μmol/L. The activities of LDH、HKand PK of test groups were lower than the control group’s,as well as theexpressions of Akt mRNA and Myc mRNA. Cells apoptosis obviously,andcell cycles were blocked in G2and S phase. Both combined and sequencewith ABZ can decrease action concentration of DDP、EPI and5-Fu toSKOV3/DDP cells，in a dose-and time-dependent manner,moreover,theeffect of combined was better than sequence.After treatment with ABZ，theexpression of P-gp decreased in a dose-and time-dependent manner.Conclusion：ABZ can induce the death of SKOV-3/DDP,reverse thechemoresistance and downregulation the P-gp expression by inhibitionactivities of glycolytic enzymes and the expressions of glycolysis-relatedgenes in vitro.