目的：研究腺病毒介导的重组人血管抑素 Plasminogen K5基因对乳腺癌的治疗作用。方法：通过PCR将人血纤维蛋白酶原的信号肽基因加至Plasminogen的K5结构域基因，克隆到质粒pCA13，并在293细胞中同源重组，得到腺病毒Ad-K5。将Ad-K5体外感染乳腺癌细胞B-Cap-37和血管内皮细胞ECV304，观察其对细胞生长的影响，同时在乳腺癌的裸鼠动物模型上，检测其对肿瘤生长的抑制作用。结果：在感染Ad-K5的B-Cap-37细胞中检测到K5基因mRNA的表达。Ad-K5对血管内皮细胞ECV304有抑制作用，但对癌细胞B-Cap-37没有直接抑制作用。动物实验表明Ad-K5能显著抑制肿瘤的生长。结论: K5基因能抑制乳腺癌实体瘤的生长。

Objective: To investigate the inhibitory effects of Ad-K5 on the proliferation of endothelial cells and the growth of mammary cancer.Methods: Kringle 5 of human plasminogen was constructed by PCR, and then cloned to plasmid pCA13. Recombinant adenovirus Ad-K5 was obtained through homologous recombination in 293 cells. The inhibition effect of Ad-K5 on cell proliferation was observed in vitro. The tumor size was measured at different intervals to observe the antitumoral effect of Ad-K5 in vivo.Results:The mRNA expression of K5 gene was detected in Ad-K5 infected B-Cap-37 cells. Ad-K5 inhibited the growth of ECV-304 cells, but had almost no effects on B-Cap-37 cells. It seemed that Ad-K5 could inhibit endothelial cells but not kill the cancer cells directly. Ad-K5 could also inhibit the tumor growth in vivo.Conclusion: Ad-K5 could inhibit the growth of solid mammary tumor.

R737.9

本课题受中科院95重大项目(No. KSCX2-3-06)、国家自然科学基金(No. 30120160823)和国家“863”高科技项目(No. 2001AA217031)资助。