腺病毒介导的人血管抑素基因治疗胰腺癌  

Treatment of pancreatic cancer by adenovirus mediated human angiostatin K5 gene

作　　者：潘新亭[1] 张子祥[1] 李德春[1] 朱青云[1] 朱兴国[1] 

机构地区：[1]苏州大学附属第一医院普外科,215006

出　　处：《中华实验外科杂志》2006年第10期1234-1236,F0003,共4页Chinese Journal of Experimental Surgery

基　　金：卫生部科学研究基金(WKJ2004-2-011)

摘　　要：目的观察腺病毒介导的人血管抑素基因对胰腺癌的治疗作用。方法通过病毒重组技术将人血管抑素基因克隆入增殖缺陷型腺病毒基因组中,获得腺病毒滴度达5．5×10^(10) pfu/ ml,观察转染表达后的生物学活性,通过建立裸鼠动物模型(每组数n=15例),分析基因转导后胰腺癌组织中血管抑素的表达情况及对肿瘤血管的抑制作用。结果构建了血管抑素的重组腺病毒载体pCA13-hAG；检测到血管抑素在体外mRNA水平和蛋白质水平表达率分别为87%和81%,得到279 bp电泳条带和38 000大小的蛋白条带；荷瘤裸鼠体内肿瘤体积显著低于对照组(P＜0．05),治疗组MVD为9．85±1．20,两对照组肿瘤微血管密度(MVD)分别为20．35±2．15、17,66±2．34 (P＜0．05)。结论所构建的pCA13-hAG重组腺病毒载体可有效表达具有生物学活性的血管抑素,使肿瘤内微血管生成减少,肿瘤细胞增殖减慢,为抗血管生成治疗实体瘤的临床应用奠定基础。Objective To study the inhibitory effects of adenovirus-mediated human angiostatin gene on pancreatic cancer. Methods Human angiostatin K5 gene （hAG） was cloned into the genome of replication-defective adenovirus specific for the tumor cells by virus recombination technology, and its biological activities were measured in vitro. The virus titer was 5.5 × 10^10 pfu/ml. In the nude mouse model of pancreatic cancer （n = 15） ,the expression of human angiostatin and inhibition for tumor cell in vivo. Results To construct the recombinant adenovirus vector pCA13-hAG and explore its expression in the levels of both mRNA of 279 bp and protein of 38 000. Its expression was found in 87%and 81%. It can also inhibit tumor to grow and induce tumor cell to apoptosis significantly in vivo of animal （ P 〈 0.05 ）, The intratumoral MVD also decreased significantly in the treated tumors （9.85 ± 1.20 versus 20.35 ± 2.15,17.66 ± 2.34, P 〈 0.05）. Conclusions The recombination adenovirns can express biologically active hAG effectively, which results in inhibiting the growth of micro-blood vessels and proliferation slowly. This lays the foundation for the angiogenesis therapy of the solid tumor in clinical application.

关 键 词：腺病毒 血管抑素 基因治疗 胰腺癌 

分 类 号：R735.9[医药卫生—肿瘤]