喜树碱抗肿瘤作用机制研究进展

Advances in studies on the anti-tumor mechanisms of camptothecin

喜树碱(Camptothec in CPT)能稳定拓扑异构酶Ⅰ和DNA的共价化合物,形成了三元可解离复合物,通过复制冲突模型造成DNA损伤,最终导致细胞死亡。但是DNA损伤后引起凋亡的具体分子机制还不清楚。本文简述喜树碱的可能多种抗肿瘤机制,包括不同细胞凋亡通路、信号通路,细胞周期,以及端粒损伤作用。并且CPT的作用可能是剂量和时间依赖的双相性,其抗肿瘤的作用机制也有根本上的不同。

Camptothecin can stabilize the normally transient cleavable DNA-topo I complex and forms an enzyme-drug-DNA ternary cleavable complex. The collision of the replication fork with this cleaved strand of DNA causes an irreversible arrest of replication fork, double strand DNA breakage and cell death, However the detailed mechanism of camptothecin-mediated DNA damage-induced apoptosis remains unknown. The anti-tumor effect of camptothecin is Dose- and Time-dependence. This article is an review mainly on the possible mechanism of eamptothecin involving apoptosis, cell signal transduction, cell cycle and telomeric damage and so on.