Microsomal glutathione transferase ۱ confers cisplatin resistance of non-small cell lung cancer via interaction with arachidonate lipoxygenase ۵ to repress ferroptosis
- سال انتشار: 1404
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 28، شماره: 2
- کد COI اختصاصی: JR_IJBMS-28-2_008
- زبان مقاله: انگلیسی
- تعداد مشاهده: 35
نویسندگان
Department of Thoracic Surgery, Cangzhou Central Hospital, Cangzhou۰۶۱۰۰۰, Hebei Province, P.R. China
Department of Oncology, North China Petroleum General Hospital, Cangzhou۰۶۲۵۵۰, Hebei Province, P.R. China
Department of Thoracic Surgery, Cangzhou People’s Hospital, Cangzhou۰۶۱۰۰۰, Hebei Province, P.R. China
Department of Thoracic Surgery, Huanghua People’s Hospital, Cangzhou۰۶۱۱۰۰, Hebei Province, P.R. China
Department of Oncology, Cangzhou Central Hospital, Cangzhou۰۶۱۰۰۰, Hebei Province, P.R. China
چکیده
Objective(s): Cisplatin (DDP) resistance remains a primary cause of chemotherapy failure and recurrence of non-small cell lung cancer (NSCLC). Abnormal high microsomal glutathione transferase ۱ (MGST۱) expression has been found in DDP-resistant NSCLC cells. This study aimed to explore the function and mechanism of MGST۱ in DDP resistance of NSCLC cells.Materials and Methods: The expression levels of target molecules were assessed by quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting. Cell proliferation was evaluated by cell counting kit-۸ (CCK-۸) and colony formation assays. Ferroptosis was determined by malondialdehyde (MDA), glutathione (GSH), Fe۲+, and reactive oxygen species (ROS) levels. The interaction between proteins was confirmed by Co-immunoprecipitation (Co-IP). The effect of MGST۱ on DDP resistance was evaluated using the tumor xenograft assay in vivo. Immunohistochemical staining was performed to measure Ki-۶۷ and p-H۲A.X expression in tumor tissues.Results: MGST۱ expression was higher, while arachidonate lipoxygenase ۵ (ALOX۵) expression was lower in DDP-resistant NSCLC patients and cells. MGST۱ ablation sensitized NSCLC cells to DDP therapy through inducing ferroptosis. MGST۱ protein directly interacted with ALOX۵ protein to restrain ALOX۵-triggered ferroptosis. Ferroptosis inhibitor or sh-ALOX۵ reversed the promotive effect of MGST۱ silencing on the DDP sensitivity of NSCLC cells. Finally, MGST۱ depletion sensitized NSCLC cells to DDP therapy in nude mice in vivo.Conclusion: MGST۱ high expression contributed to DDP resistance of NSCLC cells by inhibiting ALOX۵-induced ferroptosis. Our results provide a potential therapeutic target for overcoming DDP resistance in NSCLC patients.کلیدواژه ها
Acetylsalicylic acid, Antioxidants, Epididymis, Melatonin, Sperm, Testosteroneاطلاعات بیشتر در مورد COI
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