Korean J Obstet Gynecol.  2006 Oct;49(10):2137-2147.

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

Affiliations
  • 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.

Keyword

Epithelial ovarian cancer; 1-Cys peroxiredoxin; Cisplatin; Reactive oxygen species; Resistance

MeSH Terms

Antioxidants
Apoptosis
Blotting, Western
Cell Line*
Cisplatin*
Cytoplasm
Epithelial Cells
Epithelium
Female
Immunohistochemistry
In Situ Nick-End Labeling
Ovarian Neoplasms*
Ovary
Peroxiredoxins*
Plasmids
Reactive Oxygen Species
Antioxidants
Cisplatin
Peroxiredoxins
Reactive Oxygen Species
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