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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人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 therapeutic effect of adenovirus-mediated mouse endostatin gene on gastric cancer. Methods: Endostatin was cloned into the human proliferation-deficient adenovirus genome by virus recombination technique and the biological activity after transfection in vitro was observed. The animal model of human gastric cancer in nude mice was established to analyze the expression of endostatin and its inhibitory effect on tumor in animal tumor cells after gene transduction. Results: The recombinant adenovirus pcA13-mEndo expressing endostatin was constructed. The expression of endostatin mRNA and protein was detected in vitro. The chick chorioallantoic membrane assay showed that it inhibited the growth of blood vessel. Tumor-bearing nude mice tumor growth inhibition significantly. CONCLUSION: The recombinant pcA13-mEndo recombinant adenovirus vector can effectively express endostatin with bioactivity, which can reduce the tumor angiogenesis and tumor cell proliferation, and lay a foundation for the clinical application of anti-angiogenesis in the treatment of solid tumors .