去甲斑蝥素微球介入治疗对大鼠肝癌细胞凋亡和细胞增殖相关基因表达影响的研究  

Effect of interventional therapy with norcantharidin microspheres on proliferation and apoptosis-related gene expression of rat hepatic carcinoma cells

作　　者：李琦[1] 范忠泽[1] 孙珏[1] 李先茜[1] 刘晓华 顾伟[3] Paul Heng 盛霞[1] 高虹[1] 

机构地区：[1]上海中医药大学附属普陀医院肿瘤科 [2]Department of Pharmacy,National University of Singapore,Singapore 117543 [3]第二军医大学长海医院中医科

出　　处：《肿瘤》2006年第8期708-712,共5页Tumor

基　　金：上海市自然科学基金(编号:03ZR14083);上海市卫生局青年基金(编号:034Y41);中新(新加坡)国际合作项目(编号:NUS-SPT200401)

摘　　要：目的：探讨去甲斑蝥素微球介入治疗对大鼠肝癌细胞增殖和凋亡相关基因表达的影响。方法：89只肝癌大鼠随机分组后,分别经肝动脉注入生理盐水,去甲斑蝥素．空白微球,去甲斑蝥素加碘油,去甲斑蝥素微球。治疗后每组取8只观察生存时间,治疗后第8天处死余下大鼠,取肿瘤组织采用TUNEL标记法检测细胞凋亡指数,免疫组化SP法检测肝癌组织caspase-3,bcl-2,Ki67的表达。结果：治疗后N-MS(去甲斑蝥微球)组大鼠生存期明显长于其他各组(P＜0.01)。N-MS组凋亡指数和caspase-3阳性率均高于其他各组(P＜0.01)；N-MS组bcl-2阳性率和Ki67表达率低于其他各组(P＜0.01)。结论：去甲斑蝥素微球介入治疗能够延长肝癌大鼠的生存期；其介入治疗肝癌的机制与抑制Ki-67、bcl-2基因表达,上调caspase-3表达,从而抑制肝癌细胞增殖和促进细胞凋亡有关。Objective： To investigate the changes of proliferation and apoptosis-related genes in rat hepatic carcinoma cells after interventional therapy with norcantharidin microspheres（N-MS）. Methods：Eighty nine rats with hepatoma were randomly divided into five treatment groups. They were infused with normal saline 1.5 mL/kg, norcantharidin 0.43 mg/kg, bland microspheres 10 mg/kg, norcantharidin 0.43 mg/kg plus Lipi 0.8 mL/kg, and N-MS 10 mg/kg via hepatic artery, respectively. After interventional therapy, the survival time were observed on eight rats in each group. The rest rats were sacrificed on d 8 after treatment. Apoptotic index of tumor tissues was detected by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling （TUNEL） assay. Expression of caspase-3, bcl-2, and Ki-67 were measured by SP immunohistoehemical method. Results： The survival time of N-MS group was significantly longer than that of other four groups（P〈0.01）. The apoptotic index and caspase-3 positive rate in N-MS group was significantly higher than those of other four groups （P%0.01）. The positive rate of bcl-2 and expression of Ki-67 in N-MS group were significantly lower than those of other four groups （P〈0.01）. Conclusion：Interventional therapy with N-MS prolongs the survival time of the rats with hepatoma. The mechanism is related with inhibition of ceil proliferation and induction of ceil apoptosis via down-regulation of bcl-2 and Ki-67 and up-regulation of caspase-3.

关 键 词：肝肿瘤 肿瘤移植 微球体 细胞凋亡 基因表达 介入疗法 去甲斑蝥素 大鼠 

分 类 号：R735.7[医药卫生—肿瘤]