Purpose Non-small-cell lung cancer (NSCLC) is the most common form of lung cancer. Gefitinib is one of the most accepted therapies against NSCLC in those carrying EGFR mutations, but it is only effective in approximately 20% of patients with NSCLC. Thus, alternative therapeutic interventions are urgently needed to overcome gefitinib resistance. Glutaredoxin (GLRX) plays a key role in oxidative stress. However, whether GLRX inhibition could enhance gefitinib efficacy in the gefitinib-resistant NSCLC cells is unknown. In this study, we aimed to determine whether combined inhibition of GLRX could enhance growth-inhibitory effects of gefitinib in gefitinib-resistant NSCLC cells. Methods Real-time PCR and western blotting were used to examine the mRNA and protein levels of GLRX in gefitinib- sensitive PC9 and HCC827 and -resistant human lung adenocarcinoma PC9R, HCC827R, and H1975 cells. Cell Counting Kit-8, flow cytometry, JC-1 staining, and reactive oxygen species (ROS) assays were used to evaluate cell proliferation, cell cycle progression, mitochondrial membrane potential, and ROS generation, respectively. Mouse tumor xenografts were used to assess the effect of GLRX in vivo. Results We found that GLRX was upregulated in gefitinib-resistant PC9R, HCC827R, and H1975 cells. GLRX inhibition enhanced the effects of geftinib in gefitinib-resistant cell proliferation in vitro and
Journal of Cancer Research and Clinical Oncology – Springer Journals
Published: Jan 19, 2019
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