^(131)I-c(RGD)_2环肽及其联合基因治疗对荷神经胶质瘤裸鼠模型肿瘤抑制作用  

^(131)I-c(RGD)_2 Combined Lentiviral Vector E8-codA-GFP in Treatment of Human Glioblastoma in Nude Mice

作　　者：马欢[1] 刘敏[1] 陈雪祺[1] 孙宏伟[1] 闫平[1] 王荣福[1] 张春丽[1] 

机构地区：[1]北京大学第一医院,北京100034

出　　处：《肿瘤学杂志》2017年第10期837-841,共5页Journal of Chinese Oncology

基　　金：北京市自然科学基金资助项目(放射敏感性基因联合放射免疫治疗对膀胱癌的治疗作用与毒性研究)(7112129)

摘　　要：[目的]探讨^(131)I标记的c(RGD)_2 对荷神经胶质瘤裸鼠模型的治疗作用,并与放射敏感性启动子E8和CD/5-FC自杀药物系统进行联合治疗,拟建立一种具有特异性和高效性的恶性肿瘤靶向治疗方式。[方法]建立荷神经胶质瘤U87裸鼠模型30只,瘤体直径约14mm时,随机分为6组,每组5只:(1)生理盐水组;(2)^(131)I-c(RGD)_2 11.1MBq组;(3)^(131)I-c(RGD)_2 18.5MBq;(4)^(131)I-c(RGD)_2 18.5MBq+LV组:连续2d,瘤体内注射方式将5×106U/25μl的重组慢病组载体E8-cod A-GFP LV转染至肿瘤,然后通过尾静脉将18.5MBq^(131)I-c(RGD)_2 注入到小鼠体内;(5)^(131)I-c(RGD)_2 18.5MBq+LV+5-FC组:同(4),将同量慢病毒载体转染至瘤内,同时腹腔注射10 mg前体药物5-FC连续7d。(6)^(131)I-对照肽18.5MBq组(序列:YKAREC)。观察各组裸瘤肿瘤体积和质量的变化。[结果]治疗结束后,(2)、(3)、(4)、(5)、(6)组抑瘤率分别为36.75%、41.39%、43.63%、44.87%、3.31%。对瘤体质量进行比较,只有生理盐水组与(3)、(4)及(5)组之间差异有统计学意义(P<0.05),而(3)、(4)及(5)组之间差异无统计学意义(P>0.05)。[结论]^(131)I-c(RGD)_2 能抑制U87神经胶质瘤的生长,对神经胶质瘤的治疗有潜在价值。但^(131)I-c(RGD)_2 联合放射敏感性启动子E8和CD/5-FC自杀系统对于肿瘤细胞的治疗并没有达到统计学上的预期的效果,可能与开始治疗时的瘤体积过大或者样本量小有关。[Objective] To investigate the effect of 131I-c（RGD）2 combined with lentiviral vector（LV）E8-codA-GFP in treatment of human glioblastoma in nude mice. [Methods] Thirty nude mice xenografted with human blioblastoma U87 MG were randomly divided into six groups. Group1 was injected with normal saline as control group;group 2 was injected with 131I-c（RGD）2 11.1 MBq;group3 was injected with 131I-c（RGD）2 18.5 MBq;in group 4 the xenografts were infected with the lentiviral vector by intratumor injection of 2 ×108TU/25μL of E8-codA-GFP LV for 2 days and then were injected intravenously with 18.5 MBq 131I-c（RGD）2 ;in group 5 the 131I-c（RGD）2 18.5MBq and LV were given as group 4,then 10 mg prodrug 5-FC was injected i.p. for 7 days;group 6 was given 131I-scrambled peptide18.5 MBq. After 28 days the animals were sacrificed and the tumor volume,weight and net weight were measured in 6 groups. [Results] Compared to group 1,after 28 d of treatment the tumor inhibition rates in group 2,3,4,5 and 6 were 36.75%,41.39%,43.63%,44.87%,3.31%,respectively. There were significant differences in tumor weight between group 1 and groups 2,3,4,5（P〈0.05）,but no significant differences were observed among groups 2,3,4,5（P 〉0.05）. [Conclusion] 131I-c（RGD）2 can effectively inhibit tumor growth in human glioblastoma tumor bearing mice,but no synergistic effect is observed when it is combined with radiation sensitive E8 promoter and CD/5-FC suicide gene system.

关 键 词：放射敏感性启动子 CD/5-FC自杀系统 基因治疗 131I-c(RGD)2 

分 类 号：R730.264[医药卫生—肿瘤]