The Affection Of GST-∏ On Drug-sensitivity Of Gastric Cancer Cells To Platinum

IntroductionAdvanced gastric cancer is the common malignant tumor in China,which has higher mortality than the other cancers.In addition to radical surgery,chemotherapy also plays a very important role in the combined therapy.However,the existence of drug resistance impacts the therapeutic effect and prognosis intensively.Glutathione-S-transferases(GSTs)are a family of Phaseâ…¡detoxification enzymes, which exists in an organism widely.It can effluence electrophilic compounds,such as carcinogens and toxins,out of the body by catalysing the conjugation to glutathione (GSH).GST-Ï€is the most important subtype of GSTs,which is encoded by GSTP1.It is frequently overexpressed in interon cancers,so we take it as the tumor marker clinically.In most experimental systems,overexpression of GST-Ï€in cancer cells is associated with increased resistance to anticancer agents.Mutations in GSTP1 have been found to reduce the enzyme activity.Therefore,individuals with very low levels of GST activity are at increased risk for many kinds of tumors.So this study was designed to investigate the affection of GSTP1 polymorphism and expression of GST-Ï€on drug-sensitivity of gastric cancer cells to platinum.Materials and Methods1.SubjectsGastric cancer cells(MGC-803,BGC-823,SGC-7901)were cultured in RPMI 1640 medium supplemented with 10%FBS,12u/ml gentamycin.All cells were stably maintained at 37℃in a humidified atmosphere of 5%CO₂.2.MethodsGSTP1 polymorphism was detected by PCR and restriction fragment length polymorphism studies(RFLP).GST-Ï€was detected by Western Blot.Proliferation of gastric cancer cells treated by CDDP or OXA was measured by MTT assay.3.Statistical analysisEvery experiment was repeated three times.The t test were performed by SPSS software version 11.0.The statistical difference was considered significant when P＜0.05.Results1.MGC-803,BGC-823,SGC-7901 cells were all GSTP1 105Ile/Val genotype.2.MGC-803 cells didn't express GST-Ï€,BGC-823 cells expressed GST-Ï€,which was similar with SGC-7901 cells.3.The IC₅₀of MGC-803,BGC-823,SGC-7901 cells treated by CDDP or OXA for 72 hours were 0.71,1.21,1.28μg/ml,2.42,2.7,3.41μg/ml respectively.The proliferation of MGC-803 cells was lower than the other gastric cancer cells significantly.Conclusion1.MGC-803,BGC-823,SGC-7901 cells were all GSTP1 105Ile/Val genotype.2.MGC-803 cells didn't express GST-Ï€,which could have no relationship with polymorphisms in GSTP1.3.The sensitivities of the gastric cancer cells to platinum could have negative correlation with the expression of GST-Ï€,have no relationship with polymorphisms in GSTP1.4.The mechanism of multi-drug resistance in gastric cancer has the significant sense.