Association between circadian gene CLOCK and cisplatin resistance in ovarian cancer cells: A preliminary study.

Abstract

The present study aimed to observe the expression of circadian gene clock circadian regulator (CLOCK) in ovarian cancer cells and the effects of circadian gene CLOCK on cis-dichlorodiamine platinum (cisplatin) resistance in ovarian cancer cells. The expression of CLOCK mRNA and protein in cisplatin-sensitive A2780 and cisplatin-resistant CP70 cells were detected by quantitative polymerase chain reaction and western blot assay. Cisplatin-sensitive A2780 and cisplatin-resistant CP70 cells were treated with different concentrations of cisplatin for 48 h, and the expression of hCLOCK protein in the two types of cells was detected by western blot assay. RNA interference method was used to knock down the expression of CLOCK in cisplatin-resistant CP70 cells. Subsequently, the cisplatin-resistant CP70 cells were treated with cisplatin. The proliferation of cisplatin-resistant CP70 cells was observed following treatment with cisplatin. The expression of CLOCK mRNA was significantly higher in cisplatin-resistant CP70 cells (1.58±0.49) compared with cisplatin-sensitive A2780 cells (0.44±0.13) (P<0.01). Western blot assay results demonstrated that the expression of CLOCK protein was significantly greater in the cisplatin-resistant CP70 cells (1.47±0.34) compared with the cisplatin-sensitive A2780 cells (0.48±0.15) (P<0.01). Following the treatment of A2780 and CP70 cells with cisplatin, CLOCK protein expression increased with an increased concentration of cisplatin, in a dose-dependent manner (P<0.01). Following the knockdown of CLOCK in cisplatin-resistant CP70 cells by RNA interference, cisplatin treatment was able to significantly inhibit the proliferation of cells and induce apoptosis (P<0.01). The expression of circadian gene CLOCK in ovarian cancer cells was strongly associated with cisplatin resistance. The upregulation of circadian gene CLOCK in ovarian cancer cells may reduce its sensitivity to cisplatin treatment.