从DNA转录角度探讨喜树碱类药物的神经毒性

From the Perspective of DNA Transcription to Explore Neurotoxicity of Camptothecin

喜树碱类药物作为公认抗肿瘤药,其机制与抑制肿瘤细胞DNA复制过程中拓扑异构酶I(topoisomerase I,Topo-I)的活性有关。因此,分裂增殖活跃的肿瘤细胞对该类药物更为敏感。近年来,实验及临床研究均有报道,喜树碱对不具有分裂增生特性的神经元也显示出较明显的毒性作用,可引起神经元凋亡,但其机制目前并不明确。在深入分析喜树碱类药物药理作用的基础上,结合目前其神经毒性的研究进展,提出喜树碱对神经元的毒性机制可能依然与抑制Topo-I活性有关,可能是通过干扰DNA转录过程中Topo-I的活性,导致DNA转录障碍,最终引发神经元凋亡。并在该研究思路的基础上,初步提出下一步的工作设想。

Camptothecin drugs as a recognized antitumor medicine, the mechanism of its anti-tumor relates to the inhibition of the activity of topoisomerase-I which participates in tumor cell replication; Therefore, tumor cells which show proliferation activity are more sensitive to these drugs. In recent years, experimental and clinical studies have reported that eamptothecin has obviously neurotoxicity to neurons which have not split proliferation characteristics. Show that can cause neurons apoptosis, however, the mechanism is not clear at present. Based on the deeply analysis of the pharmacological activity of camptothecin drugs, combined with the current research progress of its neurotoxieity, puts forward the toxicity mechanism of camptothecin on neurons may still relevant to restrain activity of Topo-I which interferences the process of DNA transcription, and causes DNA transcription obstacles, so eventually causes neurons apoptosis. And on the basis of the research idea, puts forward the next step of work.