盐酸千金藤碱逆转肝癌多药耐药性与P-gpATP酶活性的关系研究  

Effect of cepharanthine hydrochloride on overcoming multidrug resistance and P-gp ATPase activity in mice model of hepatocellular carcinoma

作　　者：臧彩红[1,2] 张艳 江金花 王宁 韩立[1,2] 马方 王庆端 

机构地区：[1]河南省医药科学研究院,河南郑州450052 [2]郑州大学基础医学院,河南郑州450052 [3]河南省肝病药理重点实验室,河南郑州450052

出　　处：《中国药理学通报》2011年第7期1002-1006,共5页Chinese Pharmacological Bulletin

基　　金：河南省基础与前沿技术研究计划项目(No082300453204)

摘　　要：目的观察盐酸千金藤碱(cepharanthine hydrochlo-ride,CH)联合FAP对肝癌多药耐药性的逆转作用及其机制。方法 MTT法检测CH和维拉帕米对耐药细胞的无毒剂量;MTT法检测H22/FAP肝癌细胞对多柔比星、顺铂、5-氟尿嘧啶的耐药倍数;生命延长率评价CH联合FAP的药效;定磷法检测P-gp ATP酶活性。结果细胞毒性检测结果提示,CH和VER剂量分别为1.0、0.15 g.L-1时,对H22/FAP细胞的抑制率<10%;MTT检测显示,H22/FAP瘤细胞对多柔比星、顺铂、5-氟尿嘧啶的耐药倍数分别为27.75、10.20、11.20;生命延长率结果显示CH 10、5 mg.kg-1联合FAP组能有效延长小鼠生存时间;动力学分析提示CH能够提高ATP酶活性,Vmax值约为184 nmol.min-1.mg-1,与阳性对照药维拉帕米相近。结论 CH联合FAP能够逆转肝癌多药耐药性,其机制之一可能为CH能够提高P-gpATP酶活性,抑制P-gp外排功能。Aim To study the effect of cepharanthine hydrochloride on overcoming multidrug resistance in mice model of hepatocellular carcinoma.Methods Cell toxicity test and drug sensitivity test were assayed by MTT [3-（4,-5-dimethylthiazol）-2,-5-diphenylte-2H-tetrazo lium bromide].The survival time of BALB/c mice was observed by calculating life prolongation rate.The ATPase activity was observed via ATP hydrolisis.Results Cell toxicity test showed the small toxicity of CH and VER on BALB/c mice is 1.0 g·L-1 and 0.15 g·L-1 respectively;Drug sensitivity test with MTT assay showed that CH significantly enhanced cytotoxicity of adriamycin（ADR）,cis-dichlorodiamineplatinumn（CDDP）,and 5-flurouracil（5-FU） in resistance cells with resistance index（RI） of H22/FAP tumor cells 27.75,10.20,11.20 respectively.CH 10 mg·kg-1,CH 5 mg·kg-1 in combination with FAP prolonged the life of BALB/c mice with the life prolongation rate about 41.0 % and 48.8%（P0.05 vs FAP group）.The data showed CH combined with FAP agents prolonged the life of mice significantly.ATP-hydrolisis showed that CH increased ATPase activity with a Vmax of approximately 184 nmol·（min·mg）-1.Conclusion CH combined with FAP agents prolongs the life of mice significantly.One of the mechanisms may be CH in combination with FAP can upregulate the P-gp ATPase activity.

关 键 词：盐酸千金藤碱 肝癌 多药耐药 P-糖蛋白 ATP酶活性 H22细胞 H22/FAP细胞 

分 类 号：R-332[医药卫生] R284.1