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The Role of Oxidative Stress in the Development of Cisplatin Resistance in Epithelial Ovarian Cancer

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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 µmol/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.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, 275 E. Hancock, 48201, Detroit, MI, USA

    Jimmy Belotte MD, Nicole M. Fletcher PhD, Awoniyi O. Awonuga MD, Husam M. Abu-Soud PhD, Mohammed G. Saed & Ghassan M. Saed PhD

  2. Office of Graduate Scholars, Wayne State University School of Medicine, Detroit, MI, USA

    Mitchell Alexis BS

  3. Department of Obstetrics and Gynecology, Georgia Regents University, Agusta, GA, USA

    Michael P. Diamond MD

Authors
  1. Jimmy Belotte MD
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  2. Nicole M. Fletcher PhD
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  3. Awoniyi O. Awonuga MD
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  4. Mitchell Alexis BS
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  5. Husam M. Abu-Soud PhD
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  6. Mohammed G. Saed
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  7. Michael P. Diamond MD
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  8. Ghassan M. Saed PhD
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Correspondence to Ghassan M. Saed PhD.

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Belotte, J., Fletcher, N.M., Awonuga, A.O. et al. The Role of Oxidative Stress in the Development of Cisplatin Resistance in Epithelial Ovarian Cancer. Reprod. Sci. 21, 503–508 (2014). https://doi.org/10.1177/1933719113503403

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