摘要
目的:观察腺病毒介导IGF-ⅡP3启动子调控胸苷激酶对裸鼠肝癌移植瘤杀伤效应及毒性反应。方法:皮下接种HepG2建立裸鼠肝癌移植瘤模型。瘤内注射重组腺病毒,第2天腹腔注射GCV,每4天测量肿瘤体积大小,描绘肿瘤生长曲线,实验结束后处死裸鼠剥离肿瘤测量体积大小,RT-PCR方法检测肿瘤及心、肝、肾脏组织中胸苷激酶表达,常规病理学检查观察心、肝和肾脏毒性反应。结果:Ad-tkEGFP-P3+GCV治疗组裸鼠,其肿瘤生长显示被明显抑制,至第22天始,其体积明显小于其他各组(P<0.05);实验结束后剥离出的肿瘤,Ad-tkEGFP-P3+GCV组肿瘤体积明显小于其他组;只在肿瘤组织中可见有胸苷激酶特异性表达,心、肝和肾脏中未见表达;常规HE染色病理检查,显示三种重要器官结构正常,未见有炎症、变性、坏死和细胞凋亡等现象。结论:腺病毒介导IGF-ⅡP3启动子调控胸苷激酶可以抑制裸鼠肝癌移植瘤的生长,并对裸鼠无明显毒性反应,具有肝癌靶向基因治疗的可行性。
Objective： To observe the effects of adenovirus-mediated transfer of thymidine kinase gene driven by IGF-II P3 promoter and GCV system on the growth of xenografted hepatocellular carcinoma in nude mice. Methods： HepG2 cells were inoculated into nude mice to establish transplantation tumors. Ad-tkEGFP-P3 was intratumorously injected and GCV was intraperitoneally injected the next day. Tumor sizes were measured every 4 days. The nude mice were euthanized and tumors were removed on the last day. Tumor size was then measured. RT-PCR was performed to detect the tk mRNA expression in tumor, heart, liver and kidney tissue. The toxic effect was estimated by H＆E staining and pathological tests on the heart, liver and kidneys. Results： The inhibition of tumor growth in group Ad-tkEGFP-P3＋GCV nude mice was more significant compared with the other 3 groups （P〈0.05）. The tumor volumes in group Ad-tkEGFP-P3＋GCV nude mice were smaller than those of the other 3 groups. Tk mRNA could only be detected in tumor tissue, but not in heart, liver or kidney tissue. No inflammation, degeneration, necrosis nor apoptosis was observed in the heart, liver and kidneys. Conclusion： Intratumor injection of Ad-tkEGFP-P3 following GCV intraperitoneal injection could inhibit the growth of transplantation tumors in nude mice. There is no obvious toxic effect of Ad-tkEGFP-P3 following GCV treatment on nude mice.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第12期661-664,共4页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金(编号:30070853)
广东省医学科研基金资助(编号:A2008368)~~
关键词
肝癌
人胰岛素样生长因子Ⅱ
启动子
基因治疗
裸鼠
Carcinoma
Hepatocellular
Human insulin-like growth factor II
Promoter
Gene therapy
Mice
Nude
