肿瘤细胞死亡的一种新形式——铁死亡  

A New Form of Tumor Cell Death: Ferroptosis

作　　者：李春燕 孙传政[1] 宋鑫[1] LI Chun-Yan;SUN Chuan-Zheng;SONG Xin(Second Department of Head and Neck Surgery,The Third Affiliated Hospital of Kunming Medical University(Tumor Hospital of Yunnan Province),Kunming 650118,China)

机构地区：[1]昆明医科大学第三附属医院(云南省肿瘤医院)头颈外二科

出　　处：《中国生物化学与分子生物学报》2019年第11期1208-1214,共7页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金(No.81260402,No.81560470,No.81773127,No.81960543);云南省中青年学术技术带头人培养专项经费(No.2015HB086);云南省医学领军人才培养专项经费(No.L-2017025)资助~~

摘　　要：铁死亡是近年来发现的一种程序性细胞死亡新形式,其主要特征是在发生于线粒体内的铁依赖性脂质过氧化物损伤诱导的细胞死亡。铁死亡细胞在形态、蛋白质及基因水平的变化均不同于细胞凋亡、坏死和自噬。2012年,铁死亡概念首次被提出后,铁死亡逐渐成为科学研究的热点。Erastin以及RSL3是铁死亡的诱导剂,谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)是铁死亡的关键调节点,GPX4的表达量减少或活性降低均可诱导铁死亡的发生。胱氨酸-谷氨酸逆向转运蛋白(system Xc-)可将细胞内的谷氨酸排出,同时将细胞外胱氨酸转运入细胞内,促进细胞内谷胱甘肽的合成,维持GPX4酶的活性。新近的研究表明,p62-keap1-Nrf2、P53-SAT1-ALOX15是铁死亡的关键调控通路,p53、BECN1以及BAP1是铁死亡的关键调节因子。Erastin以及RSL3可以选择性杀死RAS突变的肿瘤细胞,且越来越多的研究也证明,诱导肿瘤细胞铁死亡在免疫治疗以及逆转耐药方面均有着重要作用。因此,调控肿瘤细胞铁死亡很可能成为治疗肿瘤的新手段。本文就诱导肿瘤细胞铁死亡的机制及其进展作一综述。Ferroptosis is a new form of programmed cell death discovered in recent years,which is mainly characterized by iron-dependent lipid peroxide damage-induced cell death occurring in mitochondria.The changes in morphology,protein and gene levels of ferroptosis cells are different from apoptosis,necrosis and autophagy.After the concept of ferroptosis was first proposed in 2012,it gradually became the focus of scientific research.Erastin and RSL3 are the inducers of ferroptosis.Glutathione peroxidase 4(GPX4)is the key regulator of ferroptosis,the decrease in the expression level of GPX4 or the decrease in activity can induce the occurrence of ferroptosis.The cystine-glutamate reverse transporter(system Xc-)can excrete intracellular glutamate and transport extracellular cystine into the cell,promoting the synthesis of intracellular glutathione,thereby promoting GPX4 synthesis.Recent studies have shown that p62-keap1-Nrf2,P53-SAT1-ALOX15 are key regulatory pathways for ferroptosis,and p53,BECN1 and BAP1 are key regulators of ferroptosis.Erastin and RSL3 can selectively kill RAS-mutated tumor cells,and more and more studies have shown that ferroptosis plays an important role in immunotherapy and reversal of drug resistance.In this paper,we review the mechanism and progress of ferroptosis in tumor cells.

关 键 词：铁死亡 肿瘤细胞 铁代谢 

分 类 号：R73[医药卫生—肿瘤]