Saretzki Gabriele
SCMS Gerontology, Institute of Ageing and Health, Newcastle University, General Hospital, NE4 6BE, Newcastle upon Tyne, UK.
Cancer Lett. 2003 May 15;194(2):209-19. doi: 10.1016/s0304-3835(02)00708-5.
A number of different approaches have been developed to inhibit telomerase activity in human cancer cells. Different components and types of inhibitors targeting various regulatory levels have been regarded as useful for telomerase inhibition. Most methods, however, rely on successive telomere shortening. This process is very slow and causes a long time lag between the onset of inhibition and the occurrence of senescence or apoptosis as a reversal of the immortal phenotype. Many telomerase inhibitors seem to be most efficient when combined with conventional chemotherapeutics. There are some promising approaches that seem to circumvent the slow way of telomere shortening and induce fast apoptosis in treated tumor cells. It has been demonstrated that telomerase may be involved in triggering apoptosis, but the underlying molecular mechanism remains unclear.
已经开发出多种不同方法来抑制人类癌细胞中的端粒酶活性。针对各种调控水平的不同抑制剂成分和类型被认为对端粒酶抑制有用。然而，大多数方法依赖于连续的端粒缩短。这个过程非常缓慢，并且在抑制开始与衰老或凋亡（作为永生表型的逆转）发生之间造成很长的时间延迟。许多端粒酶抑制剂与传统化疗药物联合使用时似乎最有效。有一些有前景的方法似乎可以规避端粒缓慢缩短的方式，并在处理过的肿瘤细胞中诱导快速凋亡。已经证明端粒酶可能参与触发凋亡，但其潜在的分子机制仍不清楚。
