Korean J Obstet Gynecol.  2005 Oct;48(10):2313-2320.

Clusterin confers paclitaxel resistance in ovarian cancer

• Park DC
• Yeo SG
• Mok SC

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.

Keyword

Clusterin; Ovarian cancer; Paclitaxel-sensitivity and resistance

MeSH Terms

Apoptosis
Cell Cycle
Cell Death
Cell Line
Clusterin*
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Inhibitory Concentration 50
Ovarian Neoplasms*
Paclitaxel*
RNA, Messenger
RNA, Small Interfering
Transfection
Clusterin
Paclitaxel
RNA, Messenger
RNA, Small Interfering