《生命科学》 2023, 35(10): 1288-1297

小分子化合物靶向肿瘤铁死亡的研究进展

牛鹏想¹ , 山宁宇² , 李晓博³ , 李西川¹ , 刘岭霞^1,*

¹天津师范大学生命科学学院，天津市动植物抗性重点实验室，天津 300387 ²大理大学 基础医学院，大理 671000 ³天津医科大学基础医学院免疫学系，天津 300070

摘　要：

铁死亡是一种有别于细胞凋亡、坏死的新型调节性细胞死亡方式，在肿瘤等多种疾病的发生发展中具有重要作用。与正常细胞相比，肿瘤细胞的代谢水平和铁含量较高，对铁死亡较敏感。因此，有许多小分子化合物能够作为肿瘤细胞的铁死亡诱导剂或免疫细胞的铁死亡抑制剂发挥较好的抗肿瘤作用。按照小分子化合物直接作用靶点的不同，该文重点介绍了靶向GSH-GPX4、铁相关蛋白、p53 和VDAC 的铁死亡诱导剂，和靶向免疫细胞的铁死亡抑制剂，以及这些小分子化合物调控铁死亡发挥抗肿瘤作用的机制，以期为靶向肿瘤铁死亡相关的新药研发提供理论依据，并阐述了靶向铁死亡小分子药物投入临床面临的挑战。

通讯作者：刘岭霞 , Email:liulingxia678@tjnu.edu.cn

Research progress on small molecule compounds in tumor ferroptosis regulation

NIU Peng-Xiang¹ , SHAN Ning-Yu² , LI Xiao-Bo³ , LI Xi-Chuan¹ , LIU Ling-Xia^1,*

¹Tianjin Key Laboratory of Animal and Plant Resistance, School of Life Sciences, Tianjin Normal University, Tianjin 300387, China ²College of Basic Medicine, Dali University, Dali 671000, China ³Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

Abstract:

Ferroptosis, a form of regulated cell death, is distinct from apoptosis and necrosis and plays an important role in the occurrence and development of tumors and other diseases. Compared with normal cells, tumor cells have higher metabolic levels and iron content, and are more sensitive to ferroptosis. Therefore, there are many small molecule compounds that can exert good anti-tumor effects as inducers of ferroptosis in tumor cells or inhibitors of ferroptosis in immune cells. In order to provide a theoretical basis for the development of new drugs targeting tumor ferroptosis, this article focuses on various ferroptosis inducers targeting GSH-GPX4, iron-related proteins, p53 and VDAC, and ferroptosis inhibitors targeting immune cells, as well as the mechanism by which these small molecule compounds regulate ferroptosis and exert antitumor effects, and also elaborates the challenges of clinical practice of small molecule drugs targeting ferroptosis.

Communication Author：LIU Ling-Xia , Email:liulingxia678@tjnu.edu.cn