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Korean Journal of Obstetrics & Gynecology 2005;48(7):1673-1685.
Published online July 1, 2005.
Effects of the Specific COX-2 Inhibitor, Celecoxib, on Paclitaxel-Induced Apoptosis in SK-OV-3 Epithelial Ovarian Cancer Cell Line.
Yun Gul Ahn, Sung Soo Kim, Wan Joo Chun, Byung Cheul Hwang, Young Jun Song, Eun Jung Soh, Jong Yun Hwang, Jun Sik Cho, Dong Heon Lee
1Department of Obstetrics and Gynecology, College of Medicine, Kangwon National University, Chunchon, Korea. obypf@kangwon.ac.kr
2Department of Pharmacology, College of Medicine, Kangwon National University, Chunchon, Korea.
3Department of Obstetrics and Gynecology, Gachon Medical School, Incheon, Korea.
In vitro studies have revealed that treatment of various human cancer cell lines with specific cyclooxygenase 2 (COX-2) inhibitors induces apoptotic cell death. The goal of this article is to investigate the benefits of combining COX-2 inhibitors with existing treatment modalities in the management of ovarian cancer. METHODS: In this study we sought to determine the effects of combining paclitaxel and the COX-2 inhibitor celecoxib on apoptosis of epithelial ovarian cancer (EOC) cells. SK-OV-3 cells were exposed to increasing concentrations of paclitaxel (10(-7) M, 10(-6) M and 10(-5) M) and celecoxib (10(-8) M, 10(-7) M, 10(-6) M, 10(-5) M and 10(-4) M) as well as a combination of both drugs. The activity of apoptosis was evaluated by the morphologic examination and the MTT assay. The pattern of apoptosis was also assessed by the caspase-3 activity and the fraction of cleaved PARP (poly ADP-ribose polymerase) protein. RESULTS: Single application of both drugs could significantly increase the rate of apoptosis after 24 hours of continuous exposure. But concomitant treatment of SK-OV-3 EOC cell line with paclitaxel and celecoxib resulted in marked impairment of paclitaxel-induced apoptosis. The pattern of apoptosis induced by paclitaxel on SK-OV-3 EOC cell line was caspase-3 independent. CONCLUSION: Combining COX-2 inhibitors and paclitaxel does not have an additive or synergistic tumoricidal effect. On the contrary, celecoxib treatment markedly inhibited the apoptotic effects of paclitaxel in SK-OV-3 EOC cell line.
Key Words: Ovarian cancer, Paclitaxel, Celecoxib, Apoptosis

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