目的：研究腺病毒介导的鼠内皮抑素基因对胃癌的治疗作用。方法：利用病毒重组技术将内皮抑素克隆入增殖缺陷型腺病毒基因组中，观察体外转染表达后的生物学活性。通过建立荷人胃癌的裸鼠动物模型，分析基因转导后动物肿瘤细胞中内皮抑素的表达情况及对肿瘤的抑制作用。结果：构建了表达内皮抑素的重组腺病毒载体pCA13-mEndo；检测到内皮抑素在体外的mRNA水平和蛋白质水平均有表达；鸡胚绒毛尿囊膜实验表明其对血管生长起抑制作用；荷瘤裸鼠体内肿瘤生长抑制明显。结论：所构建的pCA13-mEndo重组腺病毒载体可有效表达具有生物学活性的内皮抑素，使得肿瘤内微血管生成减少，肿瘤细胞增殖减慢，为抗血管生成方法治疗实体瘤的临床应用奠定基础。

Objective：To study the inhibitory effects on gastric cancer by adenoviral transduction of mouse endostatin gene.Methods：Mouse endostatin gene was cloned into the genome of replication-defective adenovirus specific for the tumor cells by virus recombination technology, and then its biological activities were surveyed in vitro. Animal model of gastric cancer bearing nude mice were established to assay the expression of mouse endostatin and inhibition for tumor cell in vivo. Results：To construct the recombinant adenovirus vector pCA13-mEndo and explore its expression in the levels of both mRNA and protein. The protein appearing the anti-angiogenesis activity was tested by chicken chorio-allantoic membrane assay. It can also inhibit tumor to grow and induce tumor cell to apoptosis significantly in vivo of animal. Conclusions:The recombination adenovirus can express biologically active mEndostatin 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.

R730.23

国家自然科学基金国际合作重大项目资金（30120160823）及国家“863”计划重点项目资助 （2001A217031）