端粒酶抑制剂在胶质瘤治疗中的研究现状和发展前景

The research status and development prospects of telomerase inhibitors in the treatment of glioma

端粒(telomere)是人类染色体末端一段富含TTAGGG/AATCCC碱基对和3'单链的特殊结构,其末端由Shelterin蛋白复合体封闭。细胞每次分裂后,端粒都会缩短一部分,直到到达临界值,而此时将触发双链断裂(double-strand break,DSB),引起细胞死亡。为了保障细胞的长期生存,必须具备延长端粒的机制。在正常情况下,这个机制主要存在于人类干细胞中,涉及一种名为端粒酶(telomerase)的酶,端粒酶主要由催化亚基(hTERT)和RNA(hTR)两个部分组成。大多数肿瘤细胞中都检测到了端粒酶的表达,在胶质母细胞瘤中甚至高达80%的细胞都表现出高端粒酶活性,表明以端粒酶为肿瘤治疗的靶点是极具有前景的。该文主要讨论近年来出现的端粒酶抑制剂在胶质瘤治疗中的应用。

Telomere is a special structure at the end of a human chromosome that is rich in TTAGGG/AATCCC base pairs and a 3'single strand.Its end is enclosed by the Shelterin protein complex.After each cell division,the telomeres will shorten by a certain amount until reaching a critical value,which will trigger double strand break(DSB)and cause cell death.To achieve long-term survival,cells must have the ability to elongate telomeres.Under normal circumstances,there is mainly an enzyme in human stem cells that has the function of prolonging telomeres,which is called telomerase and mainly composed of catalytic subunits(hTERT)and RNA(hTR).Telomerase expression has been detected in most tumor cells,and even up to 80%of cells in glioblastoma exhibit high telomerase activity.Using telomerase as a target for tumor treatment is highly promising.This article mainly discusses the application of telomerase inhibitors in the treatment of gliomas that have emerged in recent years.