双功能域重组FN多肽抑制癌细胞浸润能力的研究

Preliminary Study on the Inhibitory Effect of Recombinant FN Polypeptide CH50 and CH56 on the Metastasis of Tumor Cells

在制备了两个Cell Ⅰ-Hep Ⅱ 双结构域重组FN多肽(CH50和CH56)的基础上,研究其抑制肿瘤细胞浸润能力的作用。两个多肽的结构差异是CH50中删除了Cell I和HepⅡ之间的Ⅲ-11和ED-A结构顺序。CH50(ED_(50)为30.2 nmol/L)结合细胞的能力略高于CH56(ED_(50)为45.4 nmol/L)。两种多肽均可显著抑制黑色素瘤B16/F1细胞结合层粘素的能力,抑制作用相同。在体内肿瘤浸润抑制试验中,两种多肽均可显著抑制癌细胞浸润能力,使肺转移结节数降低80％左右。结果提示:Ⅲ-11和ED-A结构顺序对Cell Ⅰ-Hep Ⅱ 双结构域多肽结合细胞的能力有一定的影响,但删除Ⅲ-11和ED-A不是重组多肽抑制肿瘤转移的决定因素,Cell I和Hep Ⅱ 这两个结构域单独连接在一起是其抑制肿瘤细胞转移的结构基础。

On the basis of preparation of bifunctional-domain recombinant FN polypeptides, CH50 and CH56, we have investigated the function of these polypeptides. The combining capacity of CH50 (ED50 30. 2 nmol/L) is higher than that of CH56 (ED50 45. 4 nmol/L). Both of the polypeptides can significantly sup-press the combining of melanoma B16 cells with laminin. There was no significant difference between the in-hibitory effect of two polypeptides. In the experiments of suppressing the invasiveness in vivo, both of CH50 and CH56 significantly inhibited the invasive activity of tumor cells and reduced the number of lung metastasis by 80% or so. The results suggest that Ⅲ -11 and ED-A repeats influence, to some extent, the combining ca-pacity of Cell I -Hep Ⅱ bifunctional-domain polypeptide with cells, but the deletion of these repeats is not the determining factor of the ability of bifunctional-domain polypeptides to inhibit the metastasis of tumor. The connection of Cell I and Hep II domain alone may be the structural basis of inhibiting the metastasis of tu-mor.