新型钌多吡啶配合物诱导肝癌细胞凋亡的机制研究  

Apoptosis in hepatocellular carcinoma induced by novel ruthenium polypyridyl complexes

作　　者：梁金凤 李伟镇 李晓玲[2] 

机构地区：[1]广东省第一荣军医院药剂科,广东广州510260 [2]暨南大学生命科学技术学院,广东广州510632

出　　处：《中国药理学通报》2015年第11期1592-1597,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 21201082)

摘　　要：目的探讨钌多吡啶配合物的体内外抗肝癌活性及其作用机制。方法 MTT法筛选出高效低毒的钌配合物2b;流式细胞术分析其对细胞周期的影响;Western blot法检测p53和p21蛋白的表达水平;荷瘤裸鼠实验评价该配合物的体内抗肿瘤活性。结果钌多吡啶配合物对多种人肝癌细胞株的生长有抑制作用,其中配合物2b对肝癌细胞Hep3B的作用最明显,IC50为12.1μmol·L^(-1)。2b可以有效地诱导Hep 3B细胞凋亡,使细胞内出现了DNA断裂,染色质固缩及subG1凋亡峰的出现。同时,2b能够激活caspase-9和caspase-3,促使p53蛋白磷酸化,提高p53总蛋白和p21蛋白的表达水平。体内实验表明,配合物2b对裸鼠肿瘤的生长有明显的抑制作用。结论钌多吡啶配合物在体内外模型中均具有良好的抗肝癌活性,通过诱导肿瘤细胞凋亡而抑制其增殖。Aim To evaluate the antitumor activity of ruthenium polypyridyl complexes and the underlying mechanism. Methods The right complexes 2b were filtered with highest activity and lowest toxicity by MTT assay. The change of cell cycle was detected by flow cytometry . The expression of p53 and p21 was detected by Western blot. The in vivo antitumor activity of 2b was evaluated by the assay of tumor bearing nude mice. Results 2b potentially inhibited proliferation of a variety of hepatoma cell lines, among which Hep 3B cell was the most significant ( IC50 was 12. 1 μmol · L-1 ) . The apoptosis of Hep 3 B cell was induced by 2b, as evidenced by DNA fragmentation, chromatin condensation and appearance of subG1 peak. The ac-tivities of caspase-9 and caspase-3 were activated by 2b. The phosphorylation of p53 was induced by 2b. The expression of p53 and p21 was also up-regulated by 2b. The growth of tumor of nude mice was signifi-cantly inhibited by 2b in vivo experiment. Conclusion 2b has good in vitro and vivo antitumor activities, and it can inhibite growth of Hep 3 B cells by inducing apoptosis.

关 键 词：钌 抗肿瘤 肝癌 细胞凋亡 信号转导通路 caspas-es 

分 类 号：R-332[医药卫生] R329.25