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Korean Journal of Obstetrics & Gynecology 2006;49(10):2137-2147.
Published online October 1, 2006.
The Relationship between Expression of 1-Cys Peroxiredoxin and Resistance to Cisplatin in Epithelial Ovarian Cancer Cell Lines.
Won Duk Joo, Jang Ho Pak, Jong Hyeok Kim, Shin Hyung Lee, Dae Yeon Kim, Dae Shik Suh, Yong Man Kim, Young Tak Kim, Jung Eun Mok, Joo Hyun Nam
1Department of Obstetrics and Gynecology, University of Ulsan, College of Medicine, Seoul, Korea. hyeokkim@amc.seoul.kr
2Asan Institute for Life Sciences, University of Ulsan, College of Medicine, Seoul, Korea.
Abstract
OBJECTIVE
To investigate the relationship between expression of 1-Cys peroxiredoxin (Prx) and resistance to cisplatin in epithelial ovarian cancer cell lines. METHODS: Immunohistochemistry of 1-Cys Prx was performed on both normal ovarian tissues and the tissues of epithelial ovarian cancer. Western blot was performed to measure the expression of 1-Cys Prx in SKOV-3, OVCAR-3 and SNU-8 after treatment with cisplatin. Expression of 1-Cys Prx in SKOV-3 was also measured according to both time after treatment with cisplatin and concentration of cisplatin. The generation of reactive oxygen species (ROS) was measured with and without antioxidants in SKOV-3. SKOV-3 was transfected with 1-Cys Prx green fluorescent protein plasmid to overexpress 1-Cys Prx and TUNEL assay was performed after treatment with cisplatin to examine apoptosis. RESULTS: 1-Cys Prx was strongly expressed in both stroma and epithelium of both normal ovary and epithelial ovarian cancer, especially in the cytoplasm of epithelial cells. SNU-8 and OVCAR-3 exhibited about 1.5 fold higher expression than SKOV-3. SKOV-3 showed the peak expression at 48 hours after treatment with cisplatin and in 3 microgram/mL concentration of cisplatin. The generation of ROS was increased after treatment with cisplatin to SKOV-3 and the survival of SKOV-3 against cisplatin was correlated with the concentration of antioxidants (p<0.001). No apoptosis occurred in 1-Cys Prx overexpressed SKOV-3 cells. CONCLUSION: 1-Cys Prx was shown to increase the resistance to cisplatin in epithelial ovarian cancer cell line. The result suggests that the resistance may be due to overexpression of 1-Cys Prx, which is responsible for removal of ROS generated by cisplatin.
Key Words: Epithelial ovarian cancer, 1-Cys peroxiredoxin, Cisplatin, Reactive oxygen species, Resistance


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