Circadian Gene CLOCK Affects Drug-Resistant Gene Expression and Cell Proliferation in Ovarian Cancer SKOV3/DDP Cell Lines Through Autophagy

Cancer Biotherapy & Radiopharmaceuticals
Yang SunJia-Hua Liu

Abstract

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...Continue Reading

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Citations

Apr 9, 2019·Endocrine-related Cancer·Anna AngelousiGeorge P Chrousos
Jan 28, 2020·Experimental & Molecular Medicine·Tai-Wei ZhangLi-Bo Jiang
Jul 4, 2018·International Journal of Molecular Sciences·Ángela ÁyenHouria Boulaiz
Nov 27, 2020·The Journal of International Medical Research·Xinbei ChenHuihui Wang
Feb 8, 2021·Drug Discovery Today·Matteo Astone, Massimo M Santoro
Oct 30, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sadia RahmanElitza P Markova-Car
Feb 19, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Chit TamChi Chiu Wang

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Methods Mentioned

BETA
protein assay
fluorescence microscopy
transfections
PCR
electrophoresis
X-ray
flow cytometry
ELISA
transfection
reverse transcription-PCR

Software Mentioned

SPSS13
WinMDI2

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