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Experimental study on the mechanism of cisplatin resistance in human ovarian carcinoma cells

CHEN Wei,LI Xu,YANG Yu cong,et al Center for Clinical Molecular Biology,the First Affiliated Hospital of X i’an Medical University Xi’an 710061,P R China  
Objective:To explore the mechanism of cisplatin resistance in human ovarian cancer Methods:A cisplatin resistant human ovarian cancer cell line,HO 8910/2,was developed in vitro after prolonged drug exposure of the cisplatin sensitive parental HO 8910 cell line Drug cytotoxicities were determined using the micro tetrazolium assay The concentrations of cellular Pt were determined by atomic absorption and the levels of cellular GSH and GST by were detected spectrophotometry Cells cycle and expression of bcl 2 and P gp were analysed by flow cytometry Results:HO 8910/2 cell line exhibited a degree of resistance of approximately 6 6times compared with the parental cell line following 48h exposure to the drugs and was cross resisance to 5 FU and VCR A 44 1%reduction was observed in platinum accumulation in the selected cells after culturing with CDDP for two hours Increased levels of cellular glutathione and glutathione S transferase were found in the cisplatin resistant cells with the results of GSH(μmol/ml) 17 63±2 00vs 15 63±1 70 (P 0 05) and GST (IU/ml ) 9 67±2 05 vs 5 33±1 70 (P 0 01),respectively HO 8910/2 cells revealed a high percent of G 2/M and an overexpressed bcl 2 protein (75 9%vs 34 4%),but there was no difference in P gp expression between the two cell lines Conclusins:It is demonstrated that decreased drug accumulation,reduced susceptibility to cisplatin induced apoptosis and increased content of intracellular glutathione and activity of glutathione S transferase may contribute to the development of cellular resistance in the HO 8910/2 cells The resistance is not related to the multidrug resistant system
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