马 欢,刘 敏,陈雪祺.131I-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[J].肿瘤学杂志,2017,23(10):837-841.
131I-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
131I-c(RGD)2 Combined Lentiviral Vector E8-codA-GFP in Treatment of Human Glioblastoma in Nude Mice
投稿时间:2016-10-21  
DOI:10.11735/j.issn.1671-170X.2017.10.B001
中文关键词:  放射敏感性启动子  CD/5-FC自杀系统  基因治疗  131I-c(RGD)2
英文关键词:radiation-responsive promoter  CD/5-FC suicide system  gene therapy  131I-c(RGD)2
基金项目: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)
作者单位
马 欢 北京大学第一医院 
刘 敏 北京大学第一医院 
陈雪祺 北京大学第一医院 
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中文摘要:
      摘 要:[目的] 探讨131I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;②131I-c(RGD)2 11.1MBq组;③131I-c(RGD)2 18.5MBq;④131I-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-codA-GFP LV转染至肿瘤,然后通过尾静脉将18.5MBq 131I-c(RGD)2注入到小鼠体内;⑤131I-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。⑥131I-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] 131I-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131I-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。
英文摘要:
      Abstract:[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 2×108 TU/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 18.5 MBq and LV were given as group 4,then 10mg 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.
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