Influence of mifepristone on DNA repair genes and cisplatin sensitivity in human ovarian cancer drug-resistance cells / 中华妇产科杂志

ABSTRACT

Objective To study the changes of DNA repair genes and enhanced anti-tumor effect of cisplatin induced by mifepristone in human ovarian cancer drug resistance cells.Methods The alterations of cisplatin concentration producing 50％inhibition(IC50)in the COC1/DDP cell lines were examined by methyl thiazolyl tetrazolium(MTT)assay.RT-PCR and flow cytometry were used to analyze the changes of the mRNA of ERCC1,BRCA1,hMLH1 genes and cell cycle and apoptosis.Subcutaneous implantation of COC1/DDP was established in nude mice and the enhanced anti-tumor effect of cisplatin by mifepristone was observed in vivo.ResultsCisplatin IC50 values of COC1/DDP cell were decreased from(3.71±0.38)μg/ml to(3.18±0.46),(1.95±0.14),(0.64±0,18)μg/ml respectively when treated with 2.5,5.0,10.0 μmol/L mifepristone.Mifepristone could down-regulate the mRNA levels of ERCC1,BRCA1,hMLH1 genes and enhance G0/G1 phase block effect pf cisplatin,and 2.5,5.0,10.0 μmol/L mifepristone combined with cisplatin increased rate of cell apoptosis from 0.08％to 5.11％,9.13％and 12.24％ respectively.The percentage of inhibition of xenograft tumor volume in combined treatment group was 70.1％,which was significantly different(P＜0.05).Conclusion By down-regulating ERCC1,BRCA1,hMLH1 genes,blocking G0/G1 phase,and increasing apoptosis rate,mifepristone could enhance anti-tumor effect of cisplatin.