环化小檗碱类似物A55的抗肿瘤活性及其机制研究  

Anticancer Activity and Primary Mechanism of Cycloberberine Derivative A55

作　　者：赵午莉[1] 李阳彪[1] 何红伟[1] 宋丹青[1] 邵荣光[1] 

机构地区：[1]中国医学科学院/北京协和医学院医药生物技术研究所,北京100050

出　　处：《医学研究杂志》2014年第5期15-18,共4页Journal of Medical Research

基　　金：国家自然科学基金资助项目(81102464);国家重大新药创新科技重大专项基金资助项目(20122X09301002-001)

摘　　要：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Western blot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。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.

关 键 词：抗肿瘤 拓扑异构酶 DNA断裂 凋亡 环化小檗碱类似物A55 

分 类 号：R979.1[医药卫生—药品]