The Relationship between Expression of 1-Cys Peroxiredoxin and Resistance to Cisplatin in Epithelial Ovarian Cancer Cell Lines / 대한산부인과학회지

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.