紫杉醇靶向微管的抗肿瘤机制研究进展

Mechanism of paclitaxel's antineoplastic activity targeting microtubules:research advances

紫杉醇抗肿瘤活性已被许多实验证实,但有关其详细分子作用机制仍研究不多。本文综述了紫杉醇影响微管从而发挥抗瘤活性的详细机制,包括紫杉醇进入微管结合位点的通道、与微管蛋白对接的方式、所致微管蛋白结构变化以及微管蛋白结构变化后产生的生物活性和后续作用,如染色体定位异常、染色体融合、细胞分裂终止、诱导凋亡、影响胞内信号转导通路、细胞自噬体形成等诸方面,为研究开发新一类靶向微管的抗肿瘤药物或指导联合用药提供参考。

The activity of paclitaxel has been confirmed in many experiments.However,only a few researches concerning its molecular mechanism have been undertaken.This paper reviews the detailed mechanisms of paclitaxel in stabilizing microtubules to exert antineoplastic effects,including the entries of paclitaxel into the binding site of microtubules,the way of docking with tubulin,biological effects resulting from structural alterations in tubulin caused by paclitaxel,and the subsequent effects,such as chromosome positioning abnormalities,chromosomal integration,termination of mitosis,induction of apoptosis,influencing intracellular signaling transduction pathway,autophagy formation and some other aspects,in order to provide some information for the development of new microtubule-targeting anti-tumor drugs or combined drugs with paclitaxel.