The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer

Jimmy Belotte, Nicole M. Fletcher, Awoniyi O. Awonuga, Mitchell Alexis, Husam M. Abu-Soud, Mohammed G. Saed, Michael P. Diamond, Ghassan M. Saed

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Objective: To investigate the role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer (EOC). Methods: Two parent EOC cell lines (MDAH-2774 and SKOV-3) and their chemoresistant counterparts (cisplatin, 50 mmol/L) were used. Total RNA was extracted and subjected to real-time reverse transcriptase polymerase chain reaction to evaluate the expression of glutathione reductase (GSR) and inducible nitric oxide synthase (iNOS), as well as nitrate/nitrite levels. Analysis of variance was used for main effects and Tukey for post hoc analysis at P < .05 for statistical significance. Results: Both cisplatin resistant cell lines displayed a significant decrease in GSR messenger RNA (mRNA) levels and activity (P <.01). As compared to sensitive controls, nitrate/nitrite levels were significantly higher in SKOV-3 cisplatin resistant cells while iNOS mRNA levels were significantly higher in MDAH-2774 cisplatin resistant cells (P < .05). Conclusion: Our data suggest that the development of cisplatin resistance tilts the balance toward a pro-oxidant state in EOC.

Original languageEnglish (US)
Pages (from-to)503-508
Number of pages6
JournalReproductive Sciences
Volume21
Issue number4
DOIs
StatePublished - Apr 2014

Keywords

  • cisplatin resistance
  • epithelial ovarian cancer
  • reactive oxygen species

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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    Belotte, J., Fletcher, N. M., Awonuga, A. O., Alexis, M., Abu-Soud, H. M., Saed, M. G., Diamond, M. P., & Saed, G. M. (2014). The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer. Reproductive Sciences, 21(4), 503-508. https://doi.org/10.1177/1933719113503403