丹参酮ⅡA及其纳米粒诱导肝癌细胞凋亡及对p38MAPK、TGFβ1信号蛋白表达的影响  

Effects of tanshinoneⅡA and its nanoparticles on apoptosis and expression of p38 MAPK and TGFβ_1 signaling proteins of hepatoma cells in mice

作　　者：李琦[1] 王炎[2] 范忠泽[1] 冯年平[3] 高虹[1] 南艺蕾[3] 倪雷[2] 鲍文磊[1] 隋华[1] 

机构地区：[1]上海中医药大学附属普陀医院肿瘤科,上海200062 [2]上海中医药大学附属普陀医院普外科,上海200062 [3]上海中医药大学中药学院,上海200120

出　　处：《肿瘤》2008年第1期8-12,共5页Tumor

基　　金：上海市中医药科研基金资助项目(编号:2004J012A);上海市医学重点专科建设资助项目(编号:05II016)

摘　　要：目的:探讨丹参酮ⅡA(Tanshinone ⅡA,TSⅡA)及其纳米粒(Tanshinone ⅡA nanoparticles,TS-NP)治疗小鼠肝癌的作用及机制。方法:采用乳化溶剂挥发法制备TS-NP,建立小鼠肝癌模型,采用TUNEL标记法检测细胞凋亡率,免疫组织化学SP法检测p38促分裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)、肿瘤生长因子(tumor growth factorβ1,TGFβ1)的表达。结果:与对照组比较,TSⅡA组、TS-NP各剂量组瘤体质量显著降低(P<0.01),生存期均明显延长,肝癌细胞凋亡率升高(P<0.01)。其中与对照组比较,TS-NP组治疗作用优于等剂量的TSⅡA组,p38 MAPK表达明显高于其他各组(P<0.01),但TGFβ1的表达低于其他各组(P<0.01);肝癌组织中p38 MAPK与TGFβ1表达呈负相关(r=-0.873,P<0.001)。结论:TSⅡA及其纳米微粒能够抑制小鼠肝癌生长,延长生存期,而TS-NP的疗效优于等剂量的TSⅡA。其治疗肝癌的机制与抑制TGFβ1、上调p38 MAPK的表达从而抑制肝癌细胞增殖、诱导细胞凋亡有关质类。Objective ： To investigate the anti-tumor effects of tanshinone ⅡA （ TS ⅡA ） and its nanoparticles （TS-NP） against hepatoma in mice and possible mechanism, nethods：TS-NP was prepared by emulsion-solvent evaporation method. Hepatoma model was established in mice. The cell apoptotic index was tested by TUNEL staining, and expression of p38 mitogen activated protein kinase （p38 MAPK） and tumor growth factor β1 （TGFβ1） were detected by immunohistochemistry （SP method）. Results ：The weight of tumor in TS ⅡA and TS-NP groups at different dosages was significantly lower than that in NS group （P 〈 0.01 ） , and the survival time of mice in TS ⅡA and TS-NP groups was significantly longer than that in NS group （ P 〈0.01 ）. The apoptotic index of hepatoma cells in TS ⅡA and TS-NP groups was increased compared with NS group （P 〈0.01 ）. The therapeutic outcome was more superior in TS-NP group than TS ⅡA group at the same dosage. After treatment with TS ⅡA and TS-NP, the expression of p38 MAPK was increased, but the expression of TGFβ1 was decreased （P 〈 0.01 ）. The expression of p38 MAPK negatively correlated with TGFβ1 （r = -0. 873, P 〈 0.001 ）. Conclusion：TS ⅡA and TS-NP could inhibit the growth of hepatoma and prolong the survival time of mice. The therapeutic outcome of TS-NP-treated group is better than that of TS ⅡA-treated group at the same dosage. The anti-hepatoma mechanism may be associated with upregulation of the expression of p38 MAPK and downregulation of the expression of TGFβ1 which further inhibites cell proliferation and induces apoptosis.

关 键 词：肝肿瘤 实验性 抗肿瘤药(中药) 纳米技术 丹参酮 细胞凋亡 细胞内信号肽和蛋白质类 

分 类 号：R735.7[医药卫生—肿瘤] R73-36[医药卫生—临床医学]