Abstract B01: Superoxide dismutase significantly reversed the development of cisplatin resistance in epithelial ovarian cancer
Authors: Jimmy Belotte, Osama Nusrat, Nicole F. Fletcher, Mohammed G. Saed, Bailey Neubauer, Husam M. Abu-Soud
Journal: Clinical Cancer Research (2015)

Abstract Background: We have previously demonstrated that cisplatin resistant epithelial ovarian cancer (EOC) cells manifest a severe prooxidant state, which may be responsible for the maintenance of the resistant oncogenic phenotype. Objective: The objective of this study was to determine whether superoxide dismutase (SOD), a key antioxidant, could delay the development of cisplatin resistance in EOC cells. Methods: Human EOC cell lines, SKOV-3 and MDAH-2774 were utilized for this study. Cells were divided into three groups; untreated, cisplatin treated controls, and combined treated cisplatin plus SOD (20 U/ml). Control cells were cultured in the presence of a stepwise increase in cisplatin (0.25 μM increments every 72 hours up to a final dose of 1 μM). Combined treated cells were cultured in the same fashion as controls except for the addition of 20 U/ml SOD every 72 hours. Cells were considered resistant to cisplatin when a significantly similar or greater fold change of live cells was observed despite an increase in the concentration of cisplatin as compared to the untreated cells. The number of live and dead cells was determined every 72 hours, utilizing the Trypan blue dye exclusion method. Statistical analysis: Z-scores were used for statistical analysis at p-value &amp;lt;0.05 for significance. Z-scores probability distribution were generated from the untreated cells and cisplatin-treated cells for both MDAH-2774 and SKOV-3 lines. Results: Results: Both EOC cell lines developed cisplatin resistance at a concentration of 1 μM following several passages over a two-week period; as demonstrated by a nonstatistically significantly fold change of live cells (1.00 untreated cells vs. 1.56 cisplatin-treated controls for MDAH-2774, p&amp;gt;0.05 two-tailed; 2.81 untreated cells vs. cisplatin-treated controls 1.53 in SKOV-3, p&amp;gt;0.05 two-tailed). Similarly, combined treatment cells demonstrated cisplatin resistance at a concentration of 1 μM (1.00 untreated cells vs. 24.75 SOD+cisplatin-treated controls for MDAH-2774, p&amp;gt;0.05 two-tailed; 2.81 untreated cells vs. 1.00 SOD+cisplatin-treated controls 1.00 for SKOV-3, p&amp;gt;0.05 two-tailed). However, with increasing concentrations of SOD (40 and then 60 U/ml) there was a significant decrease in the fold change of live cells (23.75 cisplatin-treated controls versus 1.00 SOD+cisplatin-treated (p&amp;lt;0.05), 8.42 cisplatin-treated controls versus 1.00 SOD+cisplatin-treated for MDAH-2774 (p&amp;gt;0.05); 1.45 cisplatin-treated controls versus 1.00 SOD+cisplatin-treated (p&amp;gt;0.05), 1.00 SOD+cisplatin-treated versus 0.97 cisplatin-treated controls (p&amp;gt;0.05), at 40 and 60 U/ml respectively in SKOV-3). Conclusion: Our results indicate a potential role for SOD in protecting against the acquisition of chemoresistance in ovarian cancer cells and may serve as a potential therapeutic intervention in combination with chemotherapy treatment. Citation Format: Jimmy Belotte, Osama Nusrat, Nicole F. Fletcher, Mohammed G. Saed, Bailey Neubauer, Husam M. Abu-Soud. Superoxide dismutase significantly reversed the development of cisplatin resistance in epithelial ovarian cancer. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Drug Sensitivity and Resistance: Improving Cancer Therapy; Jun 18-21, 2014; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(4 Suppl): Abstract nr B01.