Nrf2/ARE pathway activation is involved in negatively regulating heat-induced apoptosis in non-small cell lung cancer cells  

作　　者：Wenyue Xie Benxu Tan Zhenzhou Yang Xian Yu Lingxiu Chen Danhua Ran Qing Xu Xiangdong Zhou 

机构地区：[1]Department of Oncology,the Second Affiliated Hospital,Chongqing Medical University,Chongqing 400010,China [2]Department of Respiratory,Chongqing Three Gorges Central Hospital,Chongqing 404000,China [3]Respiratory Department of the Elderly,Chongqing Public Health Medical Center,Chongqing 400036,China [4]Pulmonary And Critical Care Medicine Ward,Eastern Hospital,Sichuan Provincial Medical Sciences Academ y&Sichuan Provincial Peoples Hospital,Chengdu 610100,China [5]Department of Respiratory Medicine,the First Affiliated Hospital of Hainan Medical University,Haikou 570102,China

出　　处：《Acta Biochimica et Biophysica Sinica》2020年第4期439-445,共7页生物化学与生物物理学报（英文版）

基　　金：the grant from the National Natural Science Foundation of China(No.81370111).

摘　　要：Hyperthermia,particularly in combination with chemoradiotherapy,is widely used to treat various cancers.However,hyperthermia treatment is often insufficient due to thermo-tolerance.To date,the detailed mechanism underlying thermo-tolerance has not been clarified.The nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)pathway is an important cellular cytoprotective defense system that is activated by various stresses.In this study,using immunocytochemistry and western blot analysis,we demonstrated that heat stress induced Nrf2/ARE activation through the nuclear translocation of Nrf2 in non-small cell lung cancer cells.Luciferase activity was also increased.Additionally,antioxidant enzymes were increased through Nrf2 activation after heat stress.Transfection of lung cancer cells with siRNA directed against Nrf2 increased heat cytotoxicity and cell apoptosis.Heat stress could induce reactive oxygen species(ROS)accumulation,while the antioxidant NAC obviously reduced cell apoptosis ratio,indicating that heat stress induced cell apoptosis in a ROS-dependent manner.Knockdown of Nrf2 led to an abnormal elevation of ROS,and the antioxidant NAC could increase Nrf2 activation,indicating that ROS and Nrf2 act within a negative feedback loop.Taken together,these results demonstrated that Nrf2 pathway is important for maintaining resistance to heat stress,and we postulated that Nrf2 may represent a potential therapeutic target for hyperthermia in lung cancer.

关 键 词：heat stress lung cancer apoptosis NRF2 THERMO-TOLERANCE 

分 类 号：R734.2[医药卫生—肿瘤]