谷胱甘肽过氧化物酶4介导的铁死亡在非小细胞肺癌顺铂耐药中的作用  

Role of Glutathione Peroxidase 4 Mediated Ferroptosis in Cisplatin Resistance in Non-small Cell Lung Cancer

作　　者：张清峰 刘奎[1] 杨晓燕 唐波[1] 黄云[1] Zhang Qingfeng;Liu Kui;Yang Xiaoyan;Tang Bo;Huang Yun(Department of Cardiothoracic Surgery, Zigong Fourth People's Hospital, Zigong 643000, China)

机构地区：[1]自贡市第四人民医院胸心外科,自贡643000

出　　处：《成都医学院学报》2021年第5期587-590,共4页Journal of Chengdu Medical College

摘　　要：目的明确谷胱甘肽过氧化物酶4(GPX4)介导的铁死亡在非小细胞肺癌(NSCLC)顺铂(DDP)耐药中的作用。方法采用蛋白质印迹技术检测GPX4在人NSCLC细胞株(A549)和人NSCLC DDP耐药株(A549/DDP)中的表达差异;在A549细胞中过表达GPX4,在A549/DDP细胞中用铁死亡抑制剂RSL-3抑制GPX4的表达,采用CCK8试剂盒检测GPX4的表达对DDP敏感性的影响;采用活性氧自由基检测试剂盒检测ROS、采用脂质过氧化试剂盒检测Lipid ROS、CCK-8检测细胞活力等铁死亡相关标记物。结果GPX4在A549/DDP中高表达(P<0.05);DDP与RSL3均可激活A549/DDP细胞铁死亡发生,同时RSL3可抑制GPX4的表达;在A549细胞株中上调GPX4的表达,其对DDP的IC50升高(P<0.05)。结论在耐药株中抑制GPX4的表达,可促进铁死亡发生,并增强耐药株对DDP的敏感性。Objective To investigate the role of glutathione peroxidase 4(GPX4)mediated ferroptosis in DDP(cis-Diaminodichloro platinum)resistance in non-small cell lung cancer(NSCLC).Methods The differentialexpression of GPX4 in human NSCLC cell line(A549)and DDP resistant human NSCLC cell line(A549/DDP)was detected by Western blot.GPX4 was overexpressed in A549 cells,and was inhibited in A549/DDP cells by ferroptosisinhibitor RSL-3.The effect of GPX4 expression on DDP sensitivity was detected by cell counting kit-8(CCK8).Ferroptosis related markers,namely,reactive oxygen species(ROS),Lipid ROS and cell viability,were detected by ROS free radical detection kit,lipid peroxidation kit,and CCK8,respectively.Results GPX4 was highly expressed in A549/DDP cells(P<0.05).Both DDP and RSL3 could activate ferroptosis in A549/DDP cells,and RSL3 could inhibit GPX4 expression.Upregulation of GPX4 expression in A549 cells could increase their IC50 to DDP(P<0.05).Conclusion Inhibition of GPX4 expression in DDP resistant A549/DDP cells can promote ferroptosis and enhance the sensitivity of A549/DDP cells to cisplatin.

关 键 词：非小细胞肺癌 耐药 铁死亡 谷胱甘肽过氧化物酶4 

分 类 号：R73.3[医药卫生—肿瘤]