Reversal of cisplatin resistance in ovarian cancer by adenovirus-mediated RNA interference with ERCC1 gene expression in vitro
TIAN Lina1, XU Fuqiang1, JI Liqun1, LIU Xiaoping2, SHAN Yu1, YANG Feifei1, CHEN Jing2, QU Quanxin3
1.Department of Obstetrics and Gynecology, Beijing Shijingshan Hospital, Beijing 100043, China; 2. Department of Obstetrics, North China Hospital Affiliated to the University of Chinese Academy of Sciences,Qingdao 062550, China; 3.Department of Obstetrics and Gynecology, Tianjin First Central Hospital, Tianjin 300001, China
Abstract:Objective To investigate the effect of cisplatin resistance being reversed in ovarian cancer by adenovirus-mediated RNA interference with ERCC1 gene expression.Methods The cisplatin-resistant SKOV3/DDP cells were directly infected with the recombinant adenovirus, and trypan blue counting, MTT, Hoechst staining and flow cytometry were used in this study. The growth curve, doubling time, IC50 value, apoptotic morphology and cell cycle scores of SKOV3/DDP cells before and after infection were detected.Results (1) The inhibition rate of SKOV3/DDP cells was positively correlated with the concentration of cisplatin. The correlation coefficient r=0.9862 (P<0.05). The IC50 value of cisplatin was (13.93±0.37)μg/ml, and the resistance index was 1.79. (2) The sensitivity of SKOV3/DDP cells to cisplatin increased by 11.1%, 16.7%, 26.4% and 33.5% respectively in a dose-dependent manner (r=0.9716, P<0.05) after being infected with the recombinant adenovirus, and the drug resistance index decreased to 1.19. (3) The proportion of G1 phase cells, S phase cells and apoptotic rate of SKOV3/DDP cells increased (P<0.05) after being infected with the recombinant adenovirus combined with cisplatin.Conclusions Interference with ERCC1 gene expressions can reverse cisplatin resistance in cisplatin-resistant ovarian cancer cell line SKOV3/DDP cells by inducing apoptosis and regulating cell cycle distribution.
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