中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (2): 148-153.doi: 10.19401/j.cnki.1007-3639.2020.02.010

• 综述 • 上一篇    下一篇

铁死亡在肿瘤耐药中作用的研究进展

程 淇     综述 ,易晓芳  审校   

  1. 复旦大学附属妇产科医院,上海 200011
  • 出版日期:2020-02-29 发布日期:2020-03-09
  • 通信作者: 易晓芳 E-mail: yxi@fudan.edu.cn
  • 基金资助:
    国家自然科学基金(81872432)。

Research progress on ferroptosis in drug resistance of tumor

CHENG Qi, YI Xiaofang   

  1. Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
  • Online:2020-02-29 Published:2020-03-09
  • Contact: YI Xiaofang E-mail: yxi@fudan.edu.cn

摘要: 肿瘤耐药是一个多基因、多信号通路的复杂过程,越来越多的证据表明,活性氧(reactive oxygen species,ROS)失衡介导的氧化应激防御和ROS相关的铁死亡与肿瘤耐药密切相关。新近发现,肿瘤细胞可能通过负向调节铁死亡,显著增强其氧化应激防御能力,导致肿瘤耐药。铁死亡是一种铁依赖的、脂质过氧化物累积所触发驱动的一种调节性细胞死亡方式。由谷胱甘肽耗尽或谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)的失活导致的致死性代谢失衡是铁死亡过程的特征。在耐药环境下,小分子化合物诱导的铁死亡具有强烈抑制肿瘤生长的作用,可增强化疗药物敏感性,提示铁死亡在肿瘤药物耐药治疗中的作用十分重要,但有关细节仍不清楚。概述肿瘤细胞对氧化应激耐受的机制,强调铁死亡在其中的作用,并讨论肿瘤耐药治疗的策略。

关键词: 铁死亡, 化疗耐药, 铁代谢, 谷胱甘肽

Abstract: Drug resistance is a complicated process with multiple gene and signaling pathways. Multiple evidences demonstratethat reactive oxygen species (ROS) unbalance inducing oxidative stress defense and ROS-related ferroptosis are significantly involved in drug resistance. Recently, it has been found that tumor cells may significantly enhance their ability of oxidative stress defense by negatively regulating ferroptosis, leading to resistant survival. Ferroptosis is a form of regulated cell death characterized by iron-dependent accumulation of lipid hydroperoxides. The lethal metabolic imbalance caused by glutathione depletion or inactivation of glutathione peroxidase 4 (GPX4) is characteristic of it. In a drug-resistant environment, small molecule compound-induced ferroptosis strongly inhibits tumor growth and enhances chemotherapeutic drug sensitivity, suggesting the importance in the treatment of drug resistance. However, the accurate regulation of ferroptosis remains unsure. This review outlined the mechanisms of resistance to oxidative stress in tumor cells, highlighted the role of ferroptosis in drug resistance, and discussed the potential strategies for tumor drug resistance therapy.

Key words: Ferroptosis, Chemotherapy resistance, Iron metabolism, Glutathione