诱导三阴性乳腺癌发生铁死亡的化合物  

The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer

作　　者：王鑫蝶 丰大利[1] 崔祥 周素 张鹏飞 高志强 邹黎黎[2] 王君[1,4] WANG Xin-Die;FENG Da-Li;CUI Xiang;ZHOU Su;ZHANG Peng-Fei;GAO Zhi-Qiang;ZOU Li-Li;WANG Jun(Hubei Provincial Clinical Research Center for Precise Prevention and Treatment of Gastrointestinal Cancer in the Elderly&Cancer Prevention Office,The Second People’s Hospital of China Three Gorges University&The Second People’s Hospital of Yichang,Yichang 443003,China;Key Laboratory of Tumor Microenvironment and Immunotherapy at Three Gorges University&Yichang Key Laboratory of Infection and Inflammation,College of Basic Medical Sciences,China Three Gorges University,Yichang 443002,China;Department of Endocrinology,Affiliated Yiling Hospital of China Three Gorges University&Yiling People’s Hospital,Yichang 443100,China;Third-grade Pharmacological Laboratory on Traditional Chinese Medicine,State Administration of Traditional Chinese Medicine,China Three Gorges University,Yichang 443002,China)

机构地区：[1]三峡大学附属第二人民医院&宜昌市第二人民医院,湖北省老年胃肠癌精准防治临床医学研究中心&癌防办,宜昌443003 [2]三峡大学基础医学院,肿瘤微环境与免疫治疗湖北省重点实验室&宜昌市感染与炎症损伤重点实验室,宜昌443002 [3]三峡大学附属夷陵医院&宜昌市夷陵人民医院内分泌科,宜昌443100 [4]三峡大学,国家中医药管理局中药药理科研三级实验室,宜昌443002

出　　处：《生物化学与生物物理进展》2025年第4期804-819,共16页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金(81903105);湖北省老年胃肠癌精准防治临床医学研究中心开放基金(2024EGC-07,2024EGC-08);三峡大学国家中医药管理局中药药理科研三级实验室2023年度开放基金(2023PTCM07)资助项目。

摘　　要：铁死亡是近十余年发现并定义的一种程序性细胞死亡方式,主要由铁依赖的脂质过氧化诱导产生。研究表明,铁死亡参与了免疫调控、生长发育与衰老以及肿瘤抑制等多种生理功能,其在肿瘤生物学中的作用受到广泛关注。乳腺肿瘤是最常见的女性肿瘤之一,其异质性高且遗传背景复杂。其中三阴性乳腺癌是一种特殊类型的乳腺癌,缺乏传统乳腺癌治疗靶点,对现有化疗药物易产生耐药性,进展转移后治愈率低,急需寻找新型靶点或开发新药物。随着促进乳腺肿瘤铁死亡的相关研究增多,铁死亡作为乳腺癌治疗策略受到关注。已有研究发现,一些化合物和天然产物可诱导三阴性乳腺癌细胞铁死亡,抑制肿瘤增殖,并增强放疗敏感性,改善化疗耐药。本文对诱导癌细胞发生铁死亡的化合物和天然产物及其作用机制进行归纳和综述,旨在推动三阴性乳腺癌肿瘤铁死亡机制的研究,并为设计开发用于三阴性乳腺癌治疗的先导化合物提供参考。Ferroptosis,a programmed cell death modality discovered and defined in the last decade,is primarily induced by iron-dependent lipid peroxidation.At present,it has been found that ferroptosis is involved in various physiological functions such as immune regulation,growth and development,aging,and tumor suppression.Especially its role in tumor biology has attracted extensive attention and research.Breast cancer is one of the most common female tumors,characterized by high heterogeneity and complex genetic background.Triple negative breast cancer(TNBC)is a special type of breast cancer,which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis.There is an urgent need to find new targets or develop new drugs.With the increase of studies on promoting ferroptosis in breast cancer,it has gradually attracted attention as a treatment strategy for breast cancer.Some studies have found that certain compounds and natural products can act on TNBC,promote their ferroptosis,inhibit cancer cells proliferation,enhance sensitivity to radiotherapy,and improve resistance to chemotherapy drugs.To promote the study of ferroptosis in TNBC,this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action.We started with the exploration of the pathways of ferroptosis,with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism.Then,a series of compounds,including sulfasalazine(SAS),metformin,and statins,were described in terms of how they interact with cells to deplete glutathione(GSH),thereby inhibiting the activity of glutathione peroxidase 4(GPX4)and preventing the production of lipid peroxidases.The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells.We have also our focus to the realm of natural products,exploring the therapeutic potential of traditional Chinese medicine e

关 键 词：铁死亡 三阴性乳腺癌 先导化合物 中草药提取物 谷氨酸-胱氨酸反向转运体 

分 类 号：R736.3[医药卫生—肿瘤] R966[医药卫生—临床医学]