摘要
端粒是真核生物线性染色体末端的特殊结构,由端粒重复序列DNA和端粒结合蛋白组成,具有保护线性DNA末端、维持染色体稳定性等重要作用。随着细胞分裂次数的增加,端粒长度会逐渐缩短,最终引起细胞衰老或凋亡。端粒长度的维持对持续分裂的肿瘤细胞具有重要的意义。所以,端粒是肿瘤治疗的一个重要靶点,端粒长度维持机制及其相关靶向药物(端粒酶抑制剂、端粒延伸替代机制阻断剂、端粒G-四链体稳定剂以及端粒类似物T-oligo)的研究对于肿瘤治疗有着重要指导意义及临床应用价值。本文聚焦上述四个方向,对以端粒为靶点的抗肿瘤药物的最新研究进展进行综述。
Telomere is the structure at chromatin end in eucaryotic cell,which could protect linear DNA ends and stabilize genome.In human cells,telomeric DNA is 5′-TTAGGG-3′repeats binding with shelterin complex.Telomere length would be shortened along with DNA replication,and the cells would go through senescence or apoptosis when they have too short telomeres.In this case,telomere length maintenance is critical for tumor cells.Therefore,telomere is the important target for cancer therapy.The study of telomere maintenance mechanism and its related targeting drugs,such as telomerase inhibitors,alternative lengthening of telomeres blockers,telomere G-quadruplex stabilizers,and telomere analogue T-oligo,has important guiding significance and clinical application value for cancer therapy.This review focuses on the latest research progress of anticancer drugs targeting telomere.
作者
郑睿伶
韩昊益
殷星悦
张鑫
郑小辉
ZHENG Rui-Ling;HAN Hao-Yi;YIN Xing-Yue;ZHANG Xin;ZHENG Xiao-Hui(School of Pharmaceutical Science,Wenzhou Medical University,Wenzhou 325035,China)
出处
《生命科学》
CSCD
北大核心
2023年第2期148-156,共9页
Chinese Bulletin of Life Sciences
基金
国家自然科学基金项目(82273995)
浙江省自然科学基金项目(LY22H310004)
温州医科大学本科生项目(wyx2021101030)。