华东师范大学学报(自然科学版) ›› 2012, Vol. 2012 ›› Issue (3): 161-170.

• 生命科学 • 上一篇    

新型姜黄素结构衍生物抗肝癌细胞增殖作用的研究

李于博1, 文 英1, 马明亮2, 吴良春2, 文 珂2, 赵 政1   

  1. 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
  • 收稿日期:2011-03-01 修回日期:2011-06-01 出版日期:2012-05-25 发布日期:2012-05-22

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

LI Yu-bo 1, WEN Ying 1, MA Ming-liang 2, WU Liang-chun 2, WEN Ke 2, ZHAO Zheng 1   

  1. 1. Division of Pharmacology and Toxicology, Key Laboratory of Brain Functional Genomics, Ministry of Education,Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China;
    2. Division of Supermolecular Chemistry and Medicinal Chemistry, Key Laboratory of Brain Functional Genomics, Ministry of Education, Shanghai Key Laboratory of Brain Functional Genomics, East China Normal University, Shanghai 200062, China
  • Received:2011-03-01 Revised:2011-06-01 Online:2012-05-25 Published:2012-05-22

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.

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

Abstract: 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.

Key words: curcumin analogs, Bel-7402 cells, SMMC-7721 cells, apoptosis, cell cycle, caspase-3

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