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Korean Journal of Obstetrics & Gynecology 2005;48(8):1905-1916.
Published online August 1, 2005.
In Vitro Responses of SK-OV-3 Ovarian Cancer Cell Lines to Tamoxifen and Celecoxib.
Yun Gul Ahn, Sung Soo Kim, Wan Joo Chun, Il Young Cheong, 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 Anesthesiology, College of Medicine, Kangwon National University, Chunchon, Korea.
Abstract
OBJECTIVE
There are some evidences that some epithelial ovarian cancer cells respond to hormonal therapy. And in vitro studies have revealed that treatment of various human cancer cell lines with selective cyclooxygenase 2 (COX-2) inhibitors induces apoptotic cell death. The goal of this article is to evaluate the effects of tamoxifen and celecoxib, a selective COX-2 inhibitor, on the ovarian cancer cells and the benefits of combining these agents in the management of ovarian cancer. METHODS: SK-OV-3 epithelial ovarian cancer cells were exposed to increasing concentration of tamoxifen (10(-8) M, 10(-7) M, 10(-6) M, 10(-5) M and 10(-4) 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 h of continuous exposure. Concomitant treatment of SK-OV-3 cells with tamoxifen and celecoxib induced significant increase in apoptosis, comparing with single drug exposure. The pattern of apoptosis induced by these agents on SK-OV-3 cells seemed to be caspase-3 dependent. CONCLUSION: Our data suggest that combining tamoxifen with selective COX-2 inhibitor seems to have at least an additive tumoricidal effect. A more definitive role for this combination therapy in clinical settings in ovarian cancer will need to be defined through the conduct of clinical trials.
Key Words: Ovarian cancer, Tamoxifen, Celecoxib, Combination therapy
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