重组腺病毒携带人血管抑素基因抑制胰腺癌血管生成的研究  

Pancreatic cancer cell lines inhibition by adenoviral transduction carrying angiostatin gene

作　　者：潘新亭[1] 李德春[1] 朱青云[2] 张子祥[1] 朱兴国[1] 

机构地区：[1]苏州大学第一附属医院普外科,215006 [2]贵阳医学院附属医院影像研究所

出　　处：《中华普通外科杂志》2007年第3期218-221,共4页Chinese Journal of General Surgery

基　　金：卫生部科学研究基金（WKJ2004-2-011）

摘　　要：目的 研究重组腺病毒介导的人血管抑素基因（Ad—hAG）对胰腺癌血管生成的抑制作用。方法 通过病毒重组技术将人血管抑素K5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5．5×10^0pfu／ml。转染人胰腺癌细胞，Western印迹和ELISA法检测人血管抑素基因的蛋白表达情况，并通过建立荷人胰腺癌的裸鼠动物模型（每组15例），微血管密度计数分析血管抑素对胰腺癌血管形成的影响。结果 成功构建了携带血管抑素K5基因的腺病毒Ad—hAG；检测到重组腺病毒载体介导的血管抑素基因在胰腺癌细胞内高表达，微血管密度计数（MVD）治疗组为8．75±2．12。对照组MVD分别为20．52±1．25、18．52±1．36（t=6．165，P〈0．05）。结论 重组腺病毒介导的血管抑素基因在体内、外均获得高效表达，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 on angiogenesis of pancreatic cancer cell lines by adenoviral transduction of human angiostatin gene（Ad-hAG）. Methods Human angiostatin K5 gene was cloned into the genome of replication-defective adenovirus specific for AsPC-1 tumor cells by virus recombination technology, and the virus titer was 5.5× 10^10 pfu/ml. Cells＇ biological activities were surveyed by Western blotting and ELISA in vitro. Nude mice model （ n = 15 ） bearing pancreatic cancer cell lines AsPC-1 were established to assay the expression of human angiostatln and tumor inhibition. Tumor microvessel density （MVD） was analyzed. Results The recombinant adenovirus vector Ad-hAG was constructed and its expression was high beth on mRNA and protein levels. The intratumoral MVD decreased significantly in the treated tumors（ 8.75 ± 2. 12 vs. 20. 52 ± 1.25.18.52 ± 1.36, t = 6. 165, P 〈 0. 05 ）. Conclusions The expression of Ad-hAG gene was high both in vitro and in vivo, it significantly inhibited the angiogenesis and growth of implanted tumors in nude mice.

关 键 词：胰腺肿瘤 血管生成抑制剂 血管抑素 腺病毒 

分 类 号：R686[医药卫生—骨科学]