铁死亡与结直肠癌治疗
Ferroptosis and colorectal cancer treatment
张文 1张妍 2郭龙 2陈帅 2吴家乐 1李晓丹 3方学红 4叶华 2刘义2
作者信息
- 1. 广东医科大学药学院,广东东莞 523808
- 2. 广东医科大学药学院/广东省天然药物研究开发重点实验室,广东 湛江 524023
- 3. 深圳市龙华区人民医院药剂科,广东深圳 518109
- 4. 深圳市龙岗区妇幼保健院药剂科,广东 深圳 518172
- 折叠
摘要
铁死亡作为一种新型程序性细胞死亡类型,参与了结直肠癌(colorectal cancer,CRC)在内的多种疾病的发生和发展.铁死亡在形态学和分子学上不同于细胞焦亡、凋亡、坏死和自噬等细胞死亡方式.随着对肿瘤细胞死亡的深入研究,诱导肿瘤铁死亡已成为抗CRC的新型治疗途径.目前,铁死亡相关基因作为生物标志物已用于CRC的早期筛查和预后评估.部分药物通过作用于CRC细胞产生大量的活性氧,触发铁死亡,从而杀死CRC细胞.甚至可通过靶向敲减铁死亡基因溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)诱导细胞铁死亡,从而破坏CRC细胞.与此同时,免疫疗法联合铁死亡可降低谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)的表达量,在一定程度上可达到逆转CRC化学治疗药物奥沙利铂的耐药性,增强奥沙利铂对CRC细胞的杀伤作用.因此,铁死亡在CRC治疗中发挥着重要作用,其未来的研究前景可观.
Abstract
Ferroptosis,a novel form of programmed cell death,is implicated in the occurrence and development of various diseases,including colorectal cancer(CRC).Morphologically and molecularly,ferroptosis is distinct from other forms of cell death such as pyroptosis,apoptosis,necrosis,and autophagy.As the understanding of tumor cell death deepens,inducing ferroptosis in tumor cells has emerged as a new therapeutic approach against CRC.Currently,ferroptosis-related genes are used as biomarkers for early screening and prognosis evaluation in CRC.Some drugs kill CRC cells by generating large amounts of reactive oxygen species,triggering ferroptosis.Targeted knockdown of ferroptosis gene solute carrier family 7 member 11(SLC7A11)can also induce ferroptosis,thereby disrupting CRC cells.Additionally,combining immunotherapy with ferroptosis by reducing the expression of glutathione peroxidase 4(GPX4)can potentially reverse resistance to the chemotherapy drug oxaliplatin and enhance its cytotoxic effects on CRC cells.Therefore,ferroptosis plays a crucial role in CRC treatment,and its future research prospects are promising.
关键词
铁死亡/结直肠癌/机制/治疗靶点Key words
ferroptosis/colorectal cancer/mechanism/therapeutic target引用本文复制引用
出版年
2024
国家科技期刊平台
NSTL
万方数据