蟾毒灵对裸鼠人肝癌移植瘤的抑制作用及对Bcl-2和Bax蛋白表达的影响  

Inhibition action of bufalin on human transplanted hepatocellular tumor and its effects on expressions of Bcl-2 and Bax proteins in nude mice

作　　者：顾伟[1] 韩克起[1] 苏永华[1] 黄雪强[1] 凌昌全[1] 

机构地区：[1]第二军医大学长海医院中医科,上海200433

出　　处：《中西医结合学报》2007年第2期155-159,共5页Journal of Chinese Integrative Medicine

基　　金：国家自然科学基金资助项目(No30600814);上海市科学技术委员会基金资助项目(No05ZR14144)

摘　　要：目的:探讨蟾毒灵对裸鼠人肝癌原位移植模型的抗肿瘤作用及对Bcl-2和Bax蛋白表达的影响。方法:建立裸鼠人肝癌原位移植模型,随机分为蟾毒灵高(1.5mg/kg)、中(1mg/kg)、低(0.5mg/kg)剂量治疗组,阿霉素8mg/kg治疗组和模型组。裸鼠人肝癌原位移植模型第25天测量肿瘤体积,取瘤组织做HE染色观察肿瘤坏死程度并行电镜观察,DNA原位末端标记法检测凋亡标记指数,免疫组化法检测肝癌组织中Bcl-2和Bax蛋白的表达。结果:蟾毒灵各剂量组肿瘤体积均较模型组明显缩小(P<0.01),生存期较阿霉素治疗组及模型组延长(P<0.05)。电镜观察到蟾毒灵各组肿瘤出现明显的细胞凋亡征象,低、中、高剂量治疗组的凋亡指数分别为5.87±2.13、8.86±2.96和10.60±3.42,明显高于阿霉素治疗组的3.28±0.98(P<0.05或P<0.01);蟾毒灵各组瘤组织的Bax表达明显增强,而Bcl-2表达无明显改变。结论:蟾毒灵对裸鼠人肝癌原位移植模型有明显的抗肿瘤作用,其作用机制可能与上调Bax表达、诱导细胞凋亡有关。Objective： To investigate the anti-tumor effect of bufalin and its regulation on Bcl-2 and Bax proteins in orthotopically transplanted tumor of human hepatocellular carcinoma in nude mice.Methods： Orthotopically transplanted tumor of human hepatocellular carcinoma was established in nude mice. The mice were randomly divided into five groups： high-dose bufalin-treated group （1.5 mg/kg）, medium-dose bufalin-treated group （1 mg/kg）, low-dose bufalin-treated group （0.5 mg/kg）, adriamycin-treated group （8.0 mg/kg）, and normal saline-treated group. After 25 days, mice were sacrificed. The tumor volume was measured, and the pathological changes of tumor tissues were detected by HE staining to observe the tumor necrosis degree. Cell morphological changes were also observed by an electron microscopy. Label index of tumor cell apoptosis was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL）, and the expressions of Bcl-2 and Bax proteins were determined by immunohistochemical method. Results： The tumor volume in the bufalin-treated groups was shrunk significantly compared with that in the normal saline-treated group （P〈0.01）. The survival time of the bufalin-treated groups was prolonged compared with that of the adriamycin-treated group and the normal saline-treated group（P〈0.05）. Apoptotic characteristics could be seen in tumor tissues of the bufalin-treated groups.The label index of tumor cell apoptosis in the bufalin-treated groups （5.87±2.13, 8.86±2.96 and 10.60±3.42 in low-, medium-and high-dose groups respectively） was higher than that in the adriamycin-treated group （3.28 ±0.98） （P〈0.05, P〈0.01）. The expression of Bax was up-regulated, while no changes were detected as to Bcl-2 protein in tumors of the bufalin-treated groups.Conclusion： Bufalin has significant anti-tumor effect on the orthotopically transplanted tumor of human hepatocellular carcinoma in nude mice. Its effect might be related to up-regulation of Bax p

关 键 词：蟾毒灵 肝癌 细胞凋亡 BCL-2 BAX 裸小鼠 

分 类 号：R735.7[医药卫生—肿瘤]