Triapine通过ROS/GSH/GPX4轴诱导A549细胞铁死亡  

Triapine induces ferroptosis via ROS/GSH/GPX4 axis in A549 cells

作　　者：张朋飞 章立华 华东 ZHANG Peng-fei;ZHANG Li-hua;HUA Dong(School of Life Sciences and Health Engineering,Jiangnan University,Wuxi,Jiangsu 214000,China;Institute of Gastrointestinal Oncology,Medical College of Xiamen University,Xiamen,Fujian 361102,China;Dept of Oncology,Wuxi People’s Hospital of Nanjing Medical University,Wuxi,Jiangsu 214000,China)

机构地区：[1]江南大学生命科学与健康工程学院,江苏无锡214000 [2]厦门大学医学院胃肠肿瘤研究所,福建厦门361102 [3]南京医科大学无锡人民医院肿瘤科,江苏无锡214000

出　　处：《中国药理学通报》2023年第5期833-838,共6页Chinese Pharmacological Bulletin

基　　金：福建省自然科学基金资助项目(No 2021J05276)。

摘　　要：目的探究Triapine诱导非小细胞肺癌细胞A549发生铁死亡的作用与机制。方法MTT实验和克隆形成实验评价Triapine对A549细胞增殖的作用;使用DCFH-DA探针分析Triapine对A549细胞内ROS水平的影响;试剂盒检测Triapine处理后A549细胞内谷胱甘肽(glutathione,GSH)和脂质过氧化物(lipid peroxides,LPO)水平变化;Western blot分析Triapine对A549细胞内谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)蛋白表达的影响;用ROS抑制剂进行干预,检测GPX4蛋白的表达和细胞活性的变化。结果Triapine能够抑制A549细胞增殖,且IC_(50)为(3.7±0.08)mg·L^(-1);Triapine能诱导A549细胞ROS累积,降低GSH水平,提升LPO含量,下调GPX4的表达;ROS抑制剂干预能恢复Triapine引起的GPX4表达降低及细胞活性下降。结论Triapine可能通过提升A549细胞内ROS水平消耗GSH,导致GPX4表达下降,诱导铁死亡发生。Aim To investigate the induction of ferroptosis of Triapine in non-small cell lung cancer cells A549,and its mechanism.Methods The effects of Triapine on the proliferation of A549 cells were assessed by MTT assay and colony formation assay;the effect of intracellular ROS levels of Triapine treated A549 cells was studied by DCFH-DA probe;the intracellular glutathione(GSH)and lipid peroxides(LPO)levels of A549 cells were detected by the kits after treating with Triapine;the effects of Triapine on the expression of glutathione peroxidase 4(GPX4)in A549 cells were analyzed by Western blot;the changes of GPX4 level and cell viability were evaluated for the cells intervened with ROS inhibitor.Results Triapine could inhibit the proliferation of A549 cells,and the IC _(50) was(3.7±0.08)mg·L^(-1);Triapine increased the production of ROS and LPO,while decreased the GSH and GPX4 levels;the decrease of GPX4 expression and cell viability caused by Triapine could be restored by ROS inhibitor intervention.Conclusions Triapine may lead to the decrease of GPX4 expression by increasing the level of ROS and consuming GSH,which induces ferroptosis in A549 cells.

关 键 词：肺癌 铁死亡 TRIAPINE GPX4 脂质过氧化物 ROS 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学] R591.1[医药卫生—基础医学] R734.2R979.1