造影剂微泡介导WT-p53基因靶向治疗肝癌的实验研究  

Basic study on targeted therapy of liver cancer using human wild - type p53 plasmid by ultrasound with ultrasonic contrast agents

作　　者：程文[1] 邵华[1] 李洁冰[1] 杨先[1] 张国强[1] 申宝忠[2] 耿敬姝[1] 

机构地区：[1]哈尔滨医科大学附属第三医院超声科,哈尔滨150081 [2]哈尔滨医科大学附属第四医院

出　　处：《实用肿瘤学杂志》2012年第4期298-301,共4页Practical Oncology Journal

基　　金：哈尔滨市科委青年科学基金（2004AFQX2008）

摘　　要：目的评估超声造影剂介导WT-p53基因靶向治疗肝癌的疗效，以寻找一种无创、高效、无毒的靶向基因导入技术。方法首先制备裸鼠肝癌皮下模型，然后将48只荷瘤裸鼠分成4组，第1组注入p53质粒；第2组注入p53质粒后超声辐照；第3组注射造影剂＋p53质粒；第4组瘤体内注入造影剂＋p53质粒后，超声辐照瘤体。利用RT-PCR、Westernblot检测p53基因和蛋白在组织中的表达情况。结果RT-PCR检测各实验组细胞内均有p53mRNA的表达。注入超声造影剂与未注入相比，经超声照射，第4组WT-p53在肝癌细胞中的表达明显高于其他对照组（P〈0．05）。结论超声辐照下，造影剂结合的含WT-p53基因质粒可靶向性促进WT-053基因在肝癌细胞中的表达。Objective To find a non - invasive, efficient and non - venomous method of gene transfec- tion by assessing whether ultrasound mediated microbubble destruction could increase human wild type p53 plas- mid delivery to liver cancer. Methods Forty - eight nude mice with liver carcinoma by chemical intoxicants were divided into four groups. After p53 plasmid was injected into the femoral vein, the tumor was not irradiated by ul- trasound in second harmonic mode in group 1, and was done in group 2. Ultrasonic contrast agents and plasmid DNA were administrated without ultrasound exposure in liver cancer in group 3 and with the exposure in group 4. RT - PCR and Western Blot were used to detect p53 mRNA expression in liver cancer cells. Results Expres- sions of p53 mRNA were detected by RT - PCR reaction in all groups. Gene expression of the liver cancer cells in group 4 was the highest and was significantly different from other groups （ P 〈 0.05 ）. Conclusion Ultrasound ir- radiation, the compounds of microbubble agent and WT - p53 have targeted inhibitive effect on the WT - p53 gene expression of hepatoma cells.

关 键 词：超声造影剂 超声照射 基因治疗 WT-p53质粒 

分 类 号：R730.59[医药卫生—肿瘤]