AdKDR-CDglyTK融合基因系统对胰腺癌血管生成的抑制作用  

Inhibitory effects of the fusion gene system AdKDR-CDglyTK on the angiogenesis of pancreatic cancer

作　　者：黄宗海[1] 韩新军[1] 厉周[1] 俞金龙[1] 李强[1] 孔恒[1] 

机构地区：[1]南方医科大学珠江医院普外科,广州510282

出　　处：《解放军医学杂志》2008年第3期266-268,278,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家863计划项目(2001AA217171);广东省自然科学基金重点项目(013072)

摘　　要：目的研究重组腺病毒介导的KDR启动子驱动的CDglyTK融合双自杀基因系统(AdKDR-CDglyTK)对胰腺癌血管生成的抑制作用。方法将20只荷人胰腺癌裸鼠随机分为4组,每组5只。Ⅰ组:注射重组腺病毒AdKDR-CDglyTK与前药5氟胞嘧啶(5-FC)、更昔洛韦(GCV);Ⅱ组:仅注射前药5-FC、GCV;Ⅲ组:仅注射重组腺病毒AdKDR-CDglyTK;Ⅳ组:空白对照,不施加任何处理。采用重组腺病毒AdKDR-CDglyTK瘤体内多点注射,5-FC与GCV腹腔内注射的方法,观察各组治疗效果;微血管密度计数(MVD)分析该系统对胰腺癌血管形成的影响;RT-PCR检测各组的肿瘤组织,以了解有无双自杀基因CDglyTK(目的基因)的表达。结果Ⅰ组裸鼠移植瘤的生长显著受到抑制,Ⅱ、Ⅲ、Ⅳ组肿瘤生长情况无明显差别。MVDⅠ、Ⅱ、Ⅲ、Ⅳ组分别为2.08±0.79,10.01±0.77,9.91±0.63,10.39±1.35,组间差异有统计学意义(F=93.29,P=0.00),Ⅱ、Ⅲ、Ⅳ组与Ⅰ组比较,差异有统计学意义(P<0.05),而Ⅱ、Ⅲ、Ⅳ组之间差异无统计学意义(P>0.05)。RT-PCR结果显示,Ⅰ、Ⅲ组的瘤组织内扩增出2.4kB的目的基因片段,而Ⅱ、Ⅳ组瘤组织内未扩增出目的基因片段。结论AdKDR-CDglyTK联合前药5-FC及GCV在体内可明显抑制裸鼠胰腺癌血管形成和肿瘤生长。Objective To study the inhibitory effects of adenovirus-mediated fusion gene system driven by KDR promoter （AdKDR-CDglyTK） on angiogenesis and growth of pancreatic cancer. Methods The nude mice model was reproduced bearing pancreatic cancer cell lines Capan-2. Twenty nude mice were randomly and equally divided into four groups.. AdKDR-CDglyTK and 5-FC/GCV were injected to the animals of group Ⅰ; group Ⅱ received 5-FC/GCV injection, group Ⅲ received AdKDR-CDglyTK injection, and group Ⅳ as control, received neither AdKDR-CDglyTK nor 5-FC/GCV. AdKDR-CDglyTK was injected directly into the tumor, while 5-FC/GCV was given by intraperitoneal injection. The treatment efficiency in each group was observed and the tumor microvessel density （MVD） was analyzed. RT-PCR was employed to examine the expression of CDglyTK in tumors. Results Tumor growth was dramatically inhibited in group Ⅰ, while no significant difference was found in group Ⅱ, group Ⅲ and group Ⅳ. The MVD in the four groups were 2.08±0. 79, 10. 01±0. 77, 9. 91±0. 63 and 10. 39±1. 35, respectively （F=93. 29, P=0. 00）. The MVD decreased significantly in group Ⅰ compared to the other three groups （ P〈0. 05）, and no apparent difference was seen in MVD among group Ⅱ, group Ⅲ and group Ⅳ （ P〉0. 05）. RT-PCR showed that a 2.4kB fragment had been amplified in the tumor tissues of groupⅠand group Ⅲ, but not in groupⅡand group Ⅳ. Concusion AdKDR-CDglyTK with 5-FC and GCV can significantly inhibit the angiogenesis and growth of implanted pancreatic cancer in nude mice.

关 键 词：胰腺肿瘤 自杀基因 腺病毒 血管生成抑制剂 

分 类 号：R730.59[医药卫生—肿瘤]