Anti-tumor Effect of Plasminogen Activator Inhibitor Derived from Shark Cartilage

用1M盐酸从鲨鱼软骨中提取抗肿瘤物质，经超滤、凝胶层析、亲和层析和十二烷基硫酸钠-聚丙烯酰胺凝胶电泳法部分纯化。该组分被称为“软骨源性纤溶酶原激活物抑制物：CD-PAI”。通过体外和体内实验检测CD-PAI对血管内皮细胞和肿瘤细胞的生理活性。在体外研究中，CD-PAI具有抑制内皮细胞增殖、迁移和管状形成的活性。CD-PAI具有抑制肿瘤细胞侵袭的活性。另一方面，CD-PAI不能抑制肿瘤细胞的增殖。在体内研究中，CD-PAI抑制了小鼠体内移植的肿瘤生长。这些结果提示CD-PAI的抑瘤机制是抗血管生成和抗肿瘤侵袭。我们认为，进一步研究CD-PAI的蛋白序列和在人体正常组织中的分布是必要的。

Anti-tumor substances were extracted from shark cartilage with 1M GuHCl and partially purified by ultrafiltration, gel-chromatography, affinity-chromatograry and SDS-PAGE. This extracted fraction was called as "Cartilage-derived plasminogen activator inhibitor: CD-PAI". The Physiological activity of the CD-PAI to endothelial cell and tumor cells were assayed by in vitro and in vivo study. In in vitro studies, the CD-PAI had inhibitory activities against endothelial cell proliferation, migration and tube formation. And also, the CD-PAI showed inhibitory activity against tumor cell invasion. On the other hand, tumor cell proliferation was not inhibited by the CD-PAI. In in vivo studies, the CD-PAI inhibited tumor growth implanted in mice. Theses results suggest that the tumor inhibitory mechanisms of the CD-PAI are anti-angiogenesis and anti-tumor invasion. We felt that further studies concerning with analysis of protein sequence and distribution of the CD-PAI in human normal tissue.