氯化两面针碱的抗肝癌活性及对DNA拓扑异构酶的影响  

Anti-hepatoma activity of nitidine chloride and its effect on topoisomerase

作　　者：刘丽敏[1] 刘华钢[1] 

机构地区：[1]广西医科大学药学院,广西南宁530021

出　　处：《中国药理学通报》2010年第4期497-500,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30760302);广西科学研究与技术开发计划项目(No桂科攻0630002-2E)

摘　　要：目的研究氯化两面针碱对肝癌HepG2裸小鼠移植瘤的抗肿瘤作用及对DNA拓扑异构酶(TOPO)活性的影响。方法建立人肝癌裸鼠皮下移植瘤模型,观察氯化两面针碱的肿瘤抑制作用。以pBR322DNA为底物,采用琼脂糖凝胶电泳检测氯化两面针碱对TOPO介导的pBR322 DNA解旋反应的影响,以及对pBR322 DNA是否具有直接断裂作用。结果氯化两面针碱2.5、5和10mg·kg-1剂量对肝癌HepG2的抑制率分别为12.06%、35.63%和60.91%,氯化两面针碱在6.25μmol·L-1时可完全抑制TopoI的催化活性,在25μmol·L-1时完全抑制TopoⅡ的催化活性。结论氯化两面针碱具有较为明显的抗肝癌活性,对DNA TOPO活性的抑制可能是其作用机制之一。Aim To investigate the anti-tumor effect of nitidine chloride（NC）on human HepG2 hepatocellular transplanted tumor in nude mice and its effect on topoisomerase.Methods The subcutaneous transplantable tumor model of human liver cancer in nude mice was established and the anti-tumor effect of NC was calculated.The effects of NC on TopoⅠ/Ⅱ mediated-pBR322 DNA relaxation were measured by using agarose gel electrophoresis.Results NC inhibited significantly the growth of hepatoma,The inhibitory rate at the dose of 2.5,5,10 mg·kg^-1 was 12.06%,35.63% and 60.91% respectively.At the concentration of 6.25 μmol·L^-1,NC completely inhibited the pBR322 DNA cleavage mediated by TopoⅠ;at the concentration of 25 μmol·L^-1,NC completely inhibited the pBR322 DNA cleavage mediated by Topo Ⅱ.Conclusion Nitidine Chloride can inhibit hepatic carcinoma growth in nude mice,The anti-tumor mechanism is probably related to the inhibitory effect on Topo.

关 键 词：两面针 氯化两面针碱 肝癌 裸小鼠 抗肿瘤 DNA拓扑异构酶 

分 类 号：R-332[医药卫生] R284.1