腺病毒介导的MDA-7/IL-24基因对裸鼠胆囊癌移植瘤的生长抑制和促凋亡作用  

Growth inhibition and apoptosis induced by adenovirus mediated MDA-7 / IL-24 gene in gallbladder carcinoma of nude mice

作　　者：贾建光[1] 郭晨旭[1] 李靖[1] 张立功[1] 王益民[1] 全志伟[2] 钱军[1] 

机构地区：[1]蚌埠医学院第一附属医院肿瘤外科 [2]上海交通大学医学院附属新华医院,上海200092

出　　处：《中国临床药理学与治疗学》2015年第11期1221-1226,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金面上项目(30972919);蚌埠医学院科技发展基金项目(Bykf12A05)

摘　　要：目的:构建胆囊癌荷瘤鼠模型,利用构建的携带人MDA-7/IL-24基因的复制缺陷型腺病毒Ad.mda-7作为载体,观察MDA-7/IL-24基因对胆囊癌荷瘤鼠的作用,为胆囊癌的基因治疗提供理论基础。方法:构建荷瘤鼠模型,将携带人MDA-7/IL-24基因的腺病毒Ad.mda-7作用于荷瘤鼠。通过观察肿瘤大小的变化来了解MDA7/IL-24基因作用后的效果。观察荷瘤鼠的生存时间,绘制生存曲线,比较各组的治疗效果。取出肿瘤通过免疫组化和TUNEL法检测肿瘤组织内凋亡相关蛋白、细胞增殖相关抗原Ki-67蛋白的表达。结果:Ad.mda-7组裸鼠胆囊癌生长抑制率明显高于PBS组和Ad.GFP组(P<0.01);Ad.mda-7组裸鼠长期生存率为62.5%,明显高于PBS组和Ad.GFP组的35%(P<0.01);Ad.mda-7组治疗后瘤细胞的凋亡率显著高于对照组(P<0.01);Ad.mda-7能够明显抑制Ki-67的表达(P<0.01)。结论:复制缺陷型重组腺病毒载体Ad.mda7能介导MDA-7/IL-24基因在人胆囊癌荷瘤鼠抑制肿瘤的生长,延长荷瘤鼠的生存时间,促进肿瘤细胞的凋亡,减少Ki-67的表达,从而提示MDA-7/IL-24基因能够减少肿瘤的复发和转移。AIM：To construct the GBC-SD tumor-bearing athymic nude mice to investigate the effect of Ad.mda-7 on GBC-SD tumor-bearing athymic nude mice,and which can provide the theory for the use of the gene mda-7/IL-24.METHODS：The mda-7/IL-24 gene was injected intratumorally into the GBC-SD tumor-bearing athymic nude mice with a replication-incompetent adenovirus vector.The volume of tumors and the survivals of GBC-SD tumor-bearing athymic nude mice were investigated.Apoptosis of cancer cells,cell proliferation-associated antigen Ki-67 was assessed and TUNNEL methods to indicate the growth suppression.RESULTS：It was confirmed that the exogenous mda-7 /IL-24 gene inhibited GBC-SD tumors and prolonged the survival time of the GBC-SD tumor-bearing athymic nude mice.The protein product was investigated by immunochemistry;the results indicated that exogenous mda-7/IL-24 could cut down the expression of the protein of Ki-67.Apoptosis of cancer cells were improved compared with the control groups.CONCLUSION：Mda-7/IL-24 induces the tumor growth suppression and prolongs the survival time of the GBC tumor-bearing athymic nude mice,cuts down the expression of the protein of Ki-67 in vivo,induces the cancer cells apoptosis,which means MDA-7 /IL-24 can be a prefect gene for gene therapy in he human gallbladder carcinoma.

关 键 词：胆囊癌 MDA-7/IL-24 基因治疗 KI-67 

分 类 号：R735.8[医药卫生—肿瘤]