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.
出处
《华东师范大学学报（自然科学版）》
CAS
CSCD
北大核心
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
