谷胱甘肽过氧化物酶2对肺腺癌侵袭转移的影响及作用机制  

GPX2 promotes the progression of lung adenocarcinoma metastasis by inhibiting the ferroptosis

作　　者：张涛[1] 张仲卫[1] 吴迪 王涛 王奇[1] 冯江涛 张澜艺 ZHANG Tao;ZHANG Zhong-wei;WU Di(Tianjin Nankai Hospital,Tianjin 301000,China)

机构地区：[1]天津市中西医结合医院(天津市南开医院),天津300100 [2]天津市中医药研究院附属医院重症医学科,天津300120

出　　处：《中国中西医结合外科杂志》2025年第2期281-286,共6页Chinese Journal of Surgery of Integrated Traditional and Western Medicine

基　　金：天津市科技计划项目(21JCQNJC00530);天津市卫生健康科技项目(TJWJ2021QN059);天津市卫生健康委员会中西医结合科研课题(2023168);天津市自然科学基金(21JCQNJC01040)。

摘　　要：目的:探讨谷胱甘肽过氧化物酶2(GPX2)对肺腺癌(LUAD)侵袭转移的影响及作用机制。方法:利用TCGA数据库分析LUAD转移癌及原发癌差异表达基因,利用GEPIA数据库分析差异表达基因在LUAD癌组织及正常组织中的表达,并分析GPX2在LUAD临床预后中的作用;用小干扰RNA转染实验敲低人肺腺癌细胞系A549及PC-9中GPX2的表达,用CCK-8和Transwell实验分别检测细胞相对活力和侵袭能力,并检测A549及PC-9细胞中还原型谷胱甘肽(GSH)与氧化型谷胱甘肽(GSSG)比值及活性氧(ROS)水平,采用铁死亡抑制剂Ferrostatin-1处理后检测A549及PC-9细胞中相对活力和侵袭能力。结果:GPX2在LUAD转移癌中的表达水平明显高于原发癌,在癌中的表达水平明显高于正常组织,GPX2的高表达与LUAD的临床分期及总生存时间密切相关,预示着不良预后。敲低GPX2的表达可显著降低A549及PC-9细胞系的增殖及侵袭能力,降低GSH/GSSG比值,升高ROS水平;铁死亡抑制剂可逆转A549及PC-9细胞系中敲低GPX2对增殖、侵袭的抑制作用。结论:GPX2表达升高促进LUAD增殖及转移,这一作用与抑制铁死亡有关。GPX2有望成为早期预测LUAD转移的分子标志物。Objective To investigate the effect and mechanism of glutathione peroxidase 2(GPX2)on the progression of lung adenocarcinoma(LUAD)metastasis.Methods The TCGA database was used to analyze differentially expressed genes and ferroptosis regulatory genes in metastatic and primary LUAD tumors;GEPIA database was used the to analyze the expression of differentially expressed genes in LUAD cancer tissue and adjacent tissues,and analyze the role of GPX2 in the clinical prognosis of LUAD;The small interfering RNA transfection experiment was used to knock down the expression of GPX2 in A549 and PC-9 cell lines,RT-qRCR and Western blotting experiments were used to detect GPX2 expression,CCK-8 experiments were used to detect the relative cell viability of A549 and PC-9 cell lines,Transwell experiments were used to detect the invasiveness of A549 and PC-9 cell lines,and the kit was used to detect the GSH/GSSG ratio and ROS level in A549 and PC-9 cell lines.The relative viability and invasiveness of A549 and PC-9 cells were measured after Ferrostatin 1,an iron death inhibitor,was used to target the iron death process.Results The expression level of GPX2 in LUAD metastatic tumors was significantly higher than that in primary tumors,and the expression level in cancer was significantly higher than that in adjacent tissues.The high expression of GPX2 is closely related to the clinical stage and overall survival time of LUAD,indicating poor prognosis.Knocking down the expression level of GPX2 can significantly reduce the proliferation and invasion ability of A549 and PC-9 cell lines,significantly reduce the GSH/GSSG ratio,and significantly increase the ROS level.At the same time,the use of ferroptosis inhibitors can reverse the proliferation and invasion inhibition effect of knocking down GPX2 in A549 and PC-9 cell lines.Conclusion The increased expression of GPX2 is an important molecular change in the metastasis of lung adenocarcinoma.GPX2 promotes the proliferation and invasion of lung adenocarcinoma through ferroptosis inhibitio

关 键 词：肺腺癌 铁死亡 谷胱甘肽过氧化物酶2 肿瘤转移 

分 类 号：R734.2[医药卫生—肿瘤]