Study on Measure of Chemosensitivities to Topotecan, Cisplatin and Taxol Theraphy in Ovarian Cancer Cell Lines: Relationship with p53 and bcl-2 Expression and Apoptosis

Huh, Chu Yeop; Lim, Myong Cheol; Suh, Byung Sun

Abstract

OBJECTIVE
The aim of this study was to evaluate Topotecan-, Cisplatin- and Taxol-induced apoptosis in five human ovarian cell lines as a measure of chemosensitiviy and relationship between apoptosis and p53 and bcl-2 gene expression.
METHODS
In this study, the author is presenting data on apoptosis induced by Topotecan, Cisplatin and Taxol in five ovarian cancer cell lines, and represent different levels of sensitivities to Topotecan, Cisplatin and Taxol. This study also includes the interaction of these chemotherapeutic agents on ovarian cancer cell lines with respect to the apoptosis and cytotoxicity assay as a quantitative measure of the efficiency of killing. Presence of the p53 and bcl-2 gene product were examined by western blotting.
RESULTS
The five cell lines represent various sensitivities to Topotecan, Cisplatin, Taxol (LD50 range of Topotecan, 30~1000 ng/ml; Cisplatin, 3~10 microgram/ml, Taxol 5~1000 nm). SKOV-3 represent a resistant cell line which was 2~30 times resistant to Topotecan, 3 times resistant to Cisplatin, and 2~200 times resistant to Taxol when compared to others. Demonstration of apoptosis correlated with the sensitivity of the cell lines to Topotecan, Cisplatin and Taxol for SNU-840 and OVCAR-3. DNA fragmentation of OVCAR-3 was uniformly present when treated with Topotecan, Cisplatin and Taxol, 24 or 48 hours. When sequencing experimetns were performed with correlated with cytotoxicity assays, except in SNU-251 cells where no signigicant difference was observed in different interactions of Topotecan, Cisplatin and Taxol. Pretreatment with Topotecan, Cisplatin at a 24 hour interval resulted in enhanced cytotoxicity. Quantitation of the fragmented DNA correlated with that seen on gel electrophoresis.
CONCLUSION
The study indicate that the ability to achieve significant cytotoxicity by Topotecan, Cisplatin and Taxol may be related to the induction of apoptosis rather than necrosis. However, outcome of these treatments depend on cellular and genetic characheristics.