Abnormal autophagy regulation affects the chemoresistance of ovarian cancer, 
during which the circadian gene clock may play a major role. In this study, RNA 
interference plasmid pSUPER-Clock and overexpression plasmid pcDNA3.1-Clock of 
CLOCK were used to stably transfect the SKOV3/DDP cells by lipofection. Upon 
screening, the in vitro transfected cell lines with pSUPER-Clock, the autophagy 
level, and G0/G1 phase cells were significantly reduced, and the expression 
levels of Clock, LC3, P-gp, and MRP2 were inhibited. In contrast, the autophagy 
level and G0/G1 phase cells in cell lines transfected with pcDNA3.1-Clock were 
significantly increased, and the expressions of Clock, LC3, P-gp, and MRP2 were 
enhanced. In comparison with the untransfected control group showed the 
percentage of apoptotic cells in SKOV3/DDP cell lines of Clock interfering 
expression group after cisplatin treatment was significantly increased while the 
survival was substantially reduced. These results indicated that inhibiting the 
circadian gene Clock expression can reverse the cisplatin resistance of ovarian 
cancer SKOV3/DDP cell lines by affecting the protein expression of drug 
resistance genes during which autophagy plays an important role. The CLOCK gene 
may be designated as a novel candidate for targeted gene therapy in 
drug-resistant ovarian cancer.