铁死亡相关机制及其在恶性肿瘤中的研究进展

Ferroptosis:Mechanism and Role in Malignant Tumors

铁死亡是一种细胞程序性死亡,在起始条件、发生机制、分子特征等方面均与其他细胞程序性死亡,如凋亡、自噬、坏死、焦亡等有明显差别。围绕磷脂氢过氧化物的合成与代谢,氧化损伤和抗氧化保护的平衡是铁死亡调控机制的核心。在恶性肿瘤中,抗氧化保护相关通路上调抑制细胞铁死亡的发生,促进肿瘤细胞在氧化应激环境中存活,并对药物产生耐受。本文总结铁死亡主要特征和相关调控机制,并梳理铁死亡在恶性肿瘤中的研究进展及在肿瘤耐药中的机制,为深入研究恶性肿瘤发生和发展提供新思路,给抗肿瘤治疗提供新靶点。

Ferroptosis is a new type of programmed cell death different from other cell death pathways such as apoptosis,autophagy,necrosis,and pyroptosis in terms of initiation,mechanisms,and molecular characteristics.As the accumulation of phospholipid hydroperoxides is the hallmark of ferroptosis,the balance between oxidative damage and antioxidant defense is critical to the regulatory mechanism of ferroptosis.In cancer,the upregulation of antioxidant defense pathways can inhibit ferroptosis,thereby promoting cancer cells to survive the oxidative stress and develop drug resistance.This review systematically introduces the main features and regulatory mechanisms of ferroptosis.In addition,we summarize the role of ferroptosis in the progression and drug resistance of malignant tumors,providing novel implications for further research on the pathogenesis of malignant tumors and discovery of new targets for anti-cancer therapy.