氧化应激在上皮性卵巢癌顺铂耐药发生中的作用。
The role of oxidative stress in the development of cisplatin resistance in epithelial ovarian cancer.
作者信息
Belotte Jimmy, Fletcher Nicole M, Awonuga Awoniyi O, Alexis Mitchell, Abu-Soud Husam M, Saed Mohammed G, Diamond Michael P, Saed Ghassan M
机构信息
1Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, MI, USA.
出版信息
Reprod Sci. 2014 Apr;21(4):503-8. doi: 10.1177/1933719113503403. Epub 2013 Sep 27.
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.
目的
探讨氧化应激在上皮性卵巢癌（EOC）顺铂耐药发生发展中的作用。
方法
使用两种亲本EOC细胞系（MDAH - 2774和SKOV - 3）及其顺铂耐药对应细胞系（顺铂，50 μmol/L）。提取总RNA并进行实时逆转录聚合酶链反应，以评估谷胱甘肽还原酶（GSR）和诱导型一氧化氮合酶（iNOS）的表达以及硝酸盐/亚硝酸盐水平。采用方差分析进行主要效应分析，Tukey法进行事后分析，P <.05具有统计学意义。
结果
两种顺铂耐药细胞系的GSR信使核糖核酸（mRNA）水平和活性均显著降低（P <.01）。与敏感对照相比，SKOV - 3顺铂耐药细胞中的硝酸盐/亚硝酸盐水平显著升高，而MDAH - 2774顺铂耐药细胞中的iNOS mRNA水平显著升高（P <.05）。
结论
我们的数据表明，顺铂耐药的发生使EOC中的平衡向促氧化状态倾斜。
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