期刊
MOLECULAR MEDICINE REPORTS
卷 12, 期 5, 页码 6635-6641出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2015.4238
关键词
CLN3; ovarian cancer; RNA interference; proliferation; apoptosis; chemosensitivity
资金
- Science Foundation for Youths of Heilongjiang Province [QC2011C122]
- Science and Technology Foundation of Department of Education, Heilongjiang Province [11551161]
- Foundation of Department of Health, Heilongjiang Province [2007-429]
CLN3 is a recently identified anti-apoptotic gene, which has been demonstrated to be highly expressed in a diverse range of cancer cell lines, including ovarian cancer. In the present study, RNA interference, mediated by a lentivirus expressing CLN3 short hairpin RNA (shRNA) was utilized to knockdown the expression of CLN3 in the A2780 human ovarian cancer cell line, and its cisplatin-resistant and carboplatin-resistant sublines, A2780/DDP and A2780/CBP cells. It was revealed that the mRNA and protein expression levels of CLN3 were significantly reduced in the CLN3-specific shRNA-transduced cells, compared with the untransduced and control shRNA-transduced cells. In addition, specific knockdown of CLN3 in these cells inhibited cell proliferation and led to cell cycle arrest at the G0/G1 phase, with eventual apoptosis. CLN3 knockdown caused increases in the levels of Bax, FAX, cleaved-caspase 3, cleaved-caspase 8 and cleaved-RARP, but decreased the level of Bcl-2. Finally, it was observed that CLN3 depletion markedly reduced the half maximum inhibitory concentration in the A2780/DDP and A2780/CBP cells. Taken together, these data suggested. that CLN3 is involved in tumorigenesis and drug resistance in ovarian cancer, and may serve as a promising therapeutic target for its treatment.
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