新型姜黄素结构衍生物抗肝癌细胞增殖作用的研究

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.

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

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 G0/ G1 phase cells decreased while the S phase and the G2/M phase cells,and the SubG1 peak increased. 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 proliferation 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 caspase-3.