新型姜黄素结构衍生物抗肝癌细胞增殖作用的研究  

Antiproliferative and apoptotic activities of novel curcumin analogs in human liver cancer cell lines

作　　者：李于博[1] 文英[1] 马明亮[2] 吴良春[2] 文珂[2] 赵政[1] 

机构地区：[1]华东师范大学脑功能基因组学教育部重点实验室,上海市脑功能基因组学重点实验室,药理毒理研究室,上海200062 [2]华东师范大学脑功能基因组学教育部重点实验室,上海市脑功能基因组学重点实验室,超分子化学与药物化学研究室,上海200062

出　　处：《华东师范大学学报（自然科学版）》2012年第3期161-170,共10页Journal of East China Normal University(Natural Science)

基　　金：脑功能基因组学教育部重点实验室;上海市脑功能基因组学重点实验室(华东师范大学)开放项目基金

摘　　要：采用MTT法对姜黄素结构衍生物(CCM系列化合物)进行抗人肝癌细胞Bel-7402和SMMC-7721活性筛选;利用流式细胞技术和荧光显微镜检测SMMC-7721细胞凋亡及周期分布;采用Western-Blot方法检测SMMC-7721中蛋白caspase-3和剪切后p17的表达.结果表明,化合物CCM-5和CCM-14抗肿瘤活性较好,其对SMMC-7721细胞的凋亡作用呈剂量依赖性,且凋亡率与阴性对照组相比有显著差异(P<0.01);化合物浓度增高时,G0/G1期细胞减少,S期以及G2/M期细胞增加,凋亡峰SubG1峰增大;两个化合物均可增强caspase-3的表达,随着浓度的提高,caspase-3的表达趋势减弱,而剪切形式p17亚基表达量逐渐提高.因此,姜黄素结构衍生物CCM-5和CCM-14能抑制人肝癌细胞SMMC-7721细胞的增殖,促进凋亡,其作用机制可能与化合物诱导caspase-3活性的增强有关.Antiproliverative and apoptotic activities of the novel curcumin analogs （CCM series） against human liver carcinoma Bal-7402 and SMMC-7721 cells were investigated by MTT assay.The cell cycle distribution and apoptosis of SMMC-7721 cells induced by CCM-5 and CCM-14 were analyzed using flow cytometry. The expressions of caspase 3 and its activated form p17 in SMMC-7721 cells were further determined by western blot. CCM-5 and CCM-14 exhibited, in a concentration-dependent manner, the stronger antiproliferative role than those of curcumin and the other CCM compounds. Their apoptotic effects on the SMMC-7721 cells were also found to be significantly elevated as compared with the control group （P〈0.01）. Cell cycle distribution appeared that, as the concentrations of the compounds increased in SMMC-7721 cells, the GO/ G1 phase cells decreased while the S phase and the G2/M phase cells, and the SubG1 peak in- creased. Furthermore, both CCM-5 and CCM-14 could activate caspase-3 expression in the SMMC-7721 cells. Collectively, our data suggest that CCM-5 and CCM-14 can restrain prolifera- tion and promote apoptosis in SMMC-7721 cell, and the molecular mechanism underlying these actions against the cancer cells of the compounds may involve in the activation of easpase-3.

关 键 词：姜黄素结构衍生物 BEL-7402细胞 SMMC-7721细胞 细胞凋亡 细胞周期 CASPASE-3 

分 类 号：R962[医药卫生—药理学]