Glutathione Peroxidase 1 Promotes NSCLC Resistance to Cisplatin via ROS-Induced Activation of PI3K/AKT Pathway

作者：Baishen Chen, Zhuojian Shen, Duoguang Wu, Xuan Xie, Xia Xu, Liangzhan Lv, Honglue Dai, Ju Chen, Xiangfeng Gan · 发表于：BioMed Research International · 年份：2019 · DOI：10.1155/2019/7640547 · 被引用次数：84 · 研究领域：Genomics, phytochemicals, and oxidative stress、Glutathione Transferases and Polymorphisms、Redox biology and oxidative stress

Purpose . Reactive oxygen species (ROS)-induced cytotoxicity is an important mechanism by which cisplatin kills tumor cells. Glutathione peroxidase family (GPXs) is an important member of antioxidant system which metabolizes intracellular ROS and maintains homeostasis of cells. Altered expressions of GPXs enzymes, especially GPX1, have been described in a variety of human cancers. However, their functional roles in cisplatin-based chemoresistance in human malignancies including non-small cell lung cancer have never been explored. Methods . A panel of NSCLC cell lines were selected for this study. GPX1 expression was detected using quantitative RT-PCR and Western blot. Cisplatin-induced cell killing was analyzed by CCK8 assay. Intracellular ROS levels were detected by fluorescence-based flow cytometry analysis. In vitro overexpression and knockdown of GPX1 expression were performed using GPX1 expression vector and siRNA approaches. Protein levels of PTEN, NF- κ B, BCL2, Bax, and phosphorylated AKT were detected with western blot analysis using specific antibodies. Results . GPX1 expression was upregulated in a subset of NSCLC cell lines resistant to cisplatin treatment. Expression vector-mediated forced overexpression of GPX1 significantly increased cisplatin resistance in NSCLC cell lines, whereas RNA inference-mediated downregulation of GPX1 could restore sensitivity to cisplatin. Overexpression of GPX1 significantly suppressed elevation of intracellular ROS and activation o...