单纯疱疹病毒TK基因介导GCV治疗人RB肿瘤的实验研究  

Studies on Thymidine Kinase Gene ( TK ) and GCV System for Treatment of Human Retinoblastoma (RB)

作　　者：刘戟[1] 敬慧娥[2] 张文[2] 廖少希 黄倩[2] 

机构地区：[1]附属第一医院移植免疫实验室 [2]华西医科大学附属第一医院临床分子生物学实验室,成都610041

出　　处：《华西医科大学学报》2000年第3期300-303,共4页Journal of West China University of Medical Sciences

基　　金：四川省跨世纪优秀青年人才基金

摘　　要：为探讨HSV－TK基因介导的GCV系统对人视网膜母细胞瘤（RB）基因治疗的有效性，利用电穿孔技术把重组逆转录病毒载体pLXSNTK导入包装细胞PA317，筛选出逆转录病毒产生细胞PA317/TK，收获病毒。体外实验：用逆转录病毒感染RB细胞，筛选出含TK基因的RB细胞（RB/TK），用GCV分别处理RB、RB/TK及不同比例的混合细胞。体内实验：建立人RB裸鼠原位异种移植模型，瘤内注射病毒液后再经GCV处理。结果：体外实验RB/TK细胞对GCV的敏感性显著高于RB细胞，并存在旁观者效应；RB荷瘤裸鼠内TK/GCV系统对RB细胞的生长也有明显的抑制作用。提示HSVTK/GCV系统有望成为人RB肿瘤的基因治疗途径。The antitumor effect of herpes simplex virus thymidine kinase (HSV－TK) /GCV system on human retinoblastoma (RB) was studied here. A r etroviral vector with tk gene (pLXSN－TK) was transduced into packaging cell lin e PA317. Recombinant retroviral was obtained and employed to infect human RB cel ls. The in vitro efficacy of TK/GCV was evaluated by survival rate of RB cells w ith and without TK transduced 5 days after treated with GCV. A nude mouse model with heteroplantation of human RB was established to examine the in vivo effica cy. Mice with RB were given an in situ injection of retrovirus followed by treat ment with GCV for 14 days (50 mg/kg). The RB/TK cells in tissue culture dish sh owed far more sensitive to GCV than RB cells .The tumors in RB mice with TK gene transduced were much smaller than those in control. The results indicate that H SV－TK/GCV system can suppress growth of RB both in vitro and in vivo. It could be a valuable method for treatment of RB patients.

关 键 词：疱疹病毒TK基因 基因治疗 视网膜母细胞瘤 

分 类 号：R739.705[医药卫生—肿瘤]