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

用1M GuHCl从鲨鱼软骨中提取抗肿瘤物质，通过超滤、凝胶层析、亲和层析和SDS-PAGE进行部分纯化。提取的部分被称为“软骨源性纤溶酶原激活物抑制剂：CD-PAI”。体外和体内研究了CD-PAI对内皮细胞和肿瘤细胞的生理活性。在体外研究中，CD-PAI对内皮细胞的增殖、迁移和成管具有抑制作用。CD-PAI对肿瘤细胞的侵袭也有抑制作用。另一方面，CD-PAI对肿瘤细胞增殖没有抑制作用。在体内研究中，CD-PAI抑制了植入小鼠体内的肿瘤生长。提示CD-PAI的抑瘤机制主要是抗血管生成和抗肿瘤侵袭。我们认为CD-PAI在人类正常组织中的蛋白序列和分布分析值得进一步研究。

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.