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Korean Journal of Obstetrics & Gynecology 2005;48(10):2313-2320.
Published online October 1, 2005.
Clusterin confers paclitaxel resistance in ovarian cancer.
Dong Choon Park, Seung Geun Yeo, Samuel C Mok
1Department of Obstetrics and Gynecology, Saint Vincent Hospital, The Catholic University of Korea.
2Department of Otolaryngology, College of Medicine, Kyung Hee University, Korea.
3Department of Obstetrics, Gynecology and Reproductive Biology, Division of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, MS, U.S.A.
Abstract
OBJECTIVE
To evaluated whether clusterin over-expression is significantly correlated with paclitaxel resistance in ovarian cancer cell lines. METHODS: Clusterin was validated by performing expression profiling analysis and subsequently, the correlation between clusterin mRNA expression levels and the IC50 of paclitaxel was tested. Transfection of clusterin was performed on SKOV3, which expressed paclitaxel-sensitivity and low level of clusterin, and transfection of clusterin siRNA on PEOH, which expressed paclitaxel-resistance and high level of clusterin, to evaluate their effect on chemo-sensitivity, apoptosis, and cell cycle by XTT assay, cell death ELISA, and flow cytometry, respectively. RESULTS: Clusterin mRNA and protein expression levels were significantly correlated with paclitaxel resistance (P<0.001). Transfection of cluterin on SKOV3 significantly decreased apoptosis and increased paclitaxel resistance. And transfection of clusterin siRNA on PEOH significantly increased paclitaxel-sensitivity (P<0.05), and shifted cells from S to G2/M phase of the cell cycle after paclitaxel treatment. CONCLUSION: These findings suggested that clusterin overexpression confers paclitaxel-resistance by the modulation of the apoptotic pathway and cell cycle progression in ovarian cancer cells.
Key Words: Clusterin, Ovarian cancer, Paclitaxel-sensitivity and resistance


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