环化小檗碱类似物A55的抗肿瘤活性及其机制研究

目的研究环化小檗碱衍生物（CBBR）A55的抗肿瘤活性及其初步抗肿瘤机制。方法利用磺酰罗丹明B（SRB）法来检测化合物的抑瘤率和半数抑制浓度（IC50），采用流式细胞分析法来检测细胞周期分布，采用拓扑异构酶抑制实验来检测A55对拓扑异构酶I活性的抑制，采用Hochest和Westernblot实验来检测细胞凋亡以及与细胞DNA断裂修复和凋亡相关的蛋白。结果化合物A55具有较强的抗肿瘤活性，主要是通过抑制拓扑异构酶I的活性来引起DNA断裂，使细胞阻滞在s期并启动凋亡来抑制细胞增殖。结论环化小檗碱新型衍生物A55是一类结构新颖，抑瘤率强，值得进一步开发的新型化合物。

Anticancer Activity and Primary Mechanism of Cycloberberine Derivative A55.

Objective To investigate the anticancer activity and the primary mechanism of cycloberberine （CBBR） derivative A55. Methods Inhibition rate and IC50 （half-inhibitory concentration） were analyzed by SRB. Flow cytometry was used to detect cell cycle distribution. Topoisomerase I （ Top I ） inhibition assay was used to analyze the effect of A55 on Top I. Hochest and Western blot assays were used to dctect apoptosis and the protein associated with apoptosis and DNA break repair. Results Compound A55 inhibited signifi- cantly cancer cells growth. The anticancer activity could be finished by cell apoptosis and cell cycle blockade at S phase induced by DNA strand break mediated by Top I inhibition. Conclusion Cycloberberine derivative A55 is a novel structure and can inhibit strongly cell proliferation. A55 could be developed and study further.