Effects of the Specific COX-2 Inhibitor, Celecoxib, on Paclitaxel-Induced Apoptosis in SK-OV-3 Epithelial Ovarian Cancer Cell Line.
- Author:
Yun Gul AHN
1
;
Sung Soo KIM
;
Wan Joo CHUN
;
Byung Cheul HWANG
;
Young Jun SONG
;
Eun Jung SOH
;
Jong Yun HWANG
;
Jun Sik CHO
;
Dong Heon LEE
Author Information
1. Department of Obstetrics and Gynecology, College of Medicine, Kangwon National University, Chunchon, Korea. obypf@kangwon.ac.kr
- Publication Type:In Vitro ; Original Article
- Keywords:
Ovarian cancer;
Paclitaxel;
Celecoxib;
Apoptosis
- MeSH:
Adenosine Diphosphate Ribose;
Apoptosis*;
Caspase 3;
Cell Death;
Cell Line*;
Cyclooxygenase 2;
Cyclooxygenase 2 Inhibitors;
Humans;
Ovarian Neoplasms*;
Paclitaxel;
Celecoxib
- From:Korean Journal of Obstetrics and Gynecology
2005;48(7):1673-1685
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
OBJECTIVE: 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.
