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肿瘤治疗:靶向物质代谢重编程诱导铁死亡

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肿瘤细胞与正常细胞在物质代谢上存在着巨大的差异,肿瘤细胞主要表现为合成代谢增加,分解代谢减少,以及物质代谢失衡。这些差异为肿瘤细胞的生长繁殖提供了必要的物质基础,也为肿瘤的治疗提供了重要的靶点。铁死亡是一种铁依赖性的细胞死亡方式,其特征是细胞内铁依赖的脂质过氧化和脂膜抗氧化系统失衡,导致过氧化脂质过度堆积,引起脂膜结构损伤和功能丧失,最终引起细胞死亡。铁死亡的调控涉及多种代谢途径,糖代谢、脂质代谢、氨基酸代谢、核苷酸代谢和铁代谢等都调控着铁死亡。肿瘤细胞为了快速生长,代谢需求比正常细胞更加旺盛。肿瘤细胞会通过代谢重编程来满足其快速增殖的物质和能量需求。代谢重编程主要表现为糖酵解和磷酸戊糖途径增强、谷氨酰胺代谢增强、核酸合成增多、铁代谢倾向于保留更多的细胞内铁等。代谢重编程伴随活性氧的产生和抗氧化体系的激活。高氧化应激的状态使得肿瘤细胞更容易发生氧化还原失衡,引起细胞内脂质过氧化,最终导致细胞发生铁死亡。因此,深入研究铁死亡的分子机制和代谢基础,有利于开发诱导铁死亡在肿瘤治疗中的新疗法。铁死亡作为一种可调节的细胞死亡方式,可通过药理学或遗传学靶向肿瘤细胞中的物质代谢诱导肿瘤细胞铁死亡,在肿瘤治疗中存在着巨大的潜在价值。本文通过总结细胞的物质代谢对铁死亡的影响以期寻找肿瘤治疗新靶点,为临床治疗提供新思路。
Tumor Therapy:Targeted Substances Metabolism Reprogramming Induces Tumor Ferroptosis
There are huge differences between tumor cells and normal cells in material metabolism,and tumor cells mainly show increased anabolism,decreased catabolism,and imbalance in substance metabolism.These differences provide the necessary material basis for the growth and reproduction of tumor cells,and also provide important targets for the treatment of tumors.Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells,resulting in excessive accumulation of lipid peroxide,causing damage to lipid membrane structure and loss of function,and ultimately cell death.The regulation of ferroptosis involves a variety of metabolic pathways,including glucose metabolism,lipid metabolism,amino acid metabolism,nucleotide metabolism and iron metabolism.In order for tumor cells to grow rapidly,their metabolic needs are more vigorous than those of normal cells.Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs.Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway,enhanced glutamine metabolism,increased nucleic acid synthesis,and iron metabolism tends to retain more intracellular iron.Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system.The state of high oxidative stress makes tumor cells more susceptible to redox imbalances,causing intracellular lipid peroxidation,which ultimately leads to ferroptosis.Therefore,in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment.Ferroptosis,as a regulated form of cell death,can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells,which has great potential value in tumor treatment.This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.

tumor therapyferroptosissubstance metabolism reprogramming

张金萍、王栎清、王默、王欣悦、牟小琴、郑锡、程创、贺靓、邹黎黎、刘晓雯

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三峡大学肿瘤微环境与免疫治疗湖北省重点实验室&基础医学院,宜昌 443002

三峡大学附属第二人民医院,湖北省老年胃肠癌精准防治临床医学研究中心,宜昌 443002

三峡大学附属第二人民医院/宜昌市第二人民医院麻醉科,宜昌 443002

肿瘤治疗 铁死亡 物质代谢重编程

湖北省自然科学基金湖北省老年胃肠癌精准防治临床医学中心开放基金湖北省老年胃肠癌精准防治临床医学中心开放基金

2022CFB7962022EGC-062022EGC-09

2024

生物化学与生物物理进展
中国科学院生物物理研究所,中国生物物理学会

生物化学与生物物理进展

CSTPCD北大核心
影响因子:0.476
ISSN:1000-3282
年,卷(期):2024.51(7)
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