Study On Autophagy In Cisplatin Resistance Of Epitheial Ovarian Cancer

ObjectiveWe use DDP’s chemical sensitivity on ovary carcinoma cell line SKOV3and drug-resistance on ovary carcinoma cell line SKOV3/DDP as a model of chemotherapy-resistance in vitro,to explore the relationship between autophagy and cisplatin-resistance in epithelial ovarian cancer. In our study,through detecting the level of autophagy expression in DDP’s chemical sensitivity on ovary carcinoma cell line SKOV3and drug-resistance on ovary carcinoma cell line SKOV3/DDP,and with3-Methyladenine(3-MA),an specific inhibitor of autophagy,inhibiting the generation of autolysosomes to know the relationship between autophagy and cisplatin-resistance in epithelial ovarian cancer,and if we inhibit autophagy with3-MA,whether the cisplatin-resistance in epithelial ovarian cancer can be reversedMethodMTT,MDC fluorescence staining and confocal laser scanning microscopy were used to detect the formation of autophagosomes in DDP’s chemical sensitivity on ovary carcinoma cell line SKOV3and drug-resistance on ovary carcinoma cell line SKOV3/DDP,pretreatment with3-MA can change the autophagic generation.To explore the relationship between autophagy and DDP’s chemical sensitivity in ovary carcinoma and decreasing autophagy can reverse drug-resistanceResults1.DDP’s IC50is3.330μg/ml on SKOV3,and14.152μg/ml on SKOV3/DDP2.pretreatment with3-MA,DDP’s IC50is3.312μg/ml on SKOV3,there is no influence in DDP’s chemical sensitivity in ovary carcinoma(P=0.221). DDP’s IC50is6.386μg/ml on SKOV3/DDP,DDP’s chemical sensitivity is higher than DDP group(P=0.000).3-MA is non-toxic to ovary carcinoma cell line SKOV3and SKOV3/DDP.3.With MDC fluorescence staining and confocal laser scanning microscopy,DDP can enhance the the formation of autophagosomes,pretreatment with3-MA,the fluorescent density and MDC-labeled particles induced by DDP decreased in the ovary carcinoma cell line SKOV3/DDP,and there is no change in DDP’s chemical sensitivity on ovary carcinoma cell line SKOV3.Through inhibition autophagy with3-MA we can enhance DDP’s chemical sensitivity in ovary carcinoma cell line SKOV3/DDP,these result suggest that the expression of autophagy has correlation with cisplatin-resistance in epithelial ovarian cancer.Conclusion1.Autophagy is connected with cisplatin-resistance in epithelial ovarian carcinoma2.Inhibition autophagy can partially reverse cisplatin-resistance in epithelial ovarian carcinoma cell line SKOV3/DDP,and there is no change in DDP’s chemical sensitivity on ovary carcinoma cell line SKOV3.