Dyr J E, Hermanová E, Slavík K, Vodrázka Z
Neoplasma. 1986;33(4):401-7.
Proteolytic cleavage of bovine fibrinogen with covalently bound methotrexate (MTX) was studied using four different proteolytic enzymes--trypsin, chymotrypsin, pepsin, and cathepsin D and the interaction of the modified fibrinogen (or fibrin) with HeLa cells was investigated. The presence of fibrin-MTX derivative did not induce any significant morphological alternations of cells. The fibrin-MTX derivative in the gel form was solubilized easily by the action of all proteinases investigated, hydrolysis of highly crosslinked denatured fibrin-MTX in suspension proceeded slower. The solubilized fibrin-MTX degradation products had a strong inhibiting effect on the growth of HeLa cells cultured in monolayer indicating the liberation of chemotherapeutically active MTX from its fibrin derivative.
使用四种不同的蛋白水解酶——胰蛋白酶、胰凝乳蛋白酶、胃蛋白酶和组织蛋白酶D，研究了与共价结合的甲氨蝶呤（MTX）的牛纤维蛋白原的蛋白水解裂解，并研究了修饰的纤维蛋白原（或纤维蛋白）与HeLa细胞的相互作用。纤维蛋白-MTX衍生物的存在未诱导细胞出现任何明显的形态学改变。凝胶形式的纤维蛋白-MTX衍生物在所有研究的蛋白酶作用下很容易溶解，悬浮液中高度交联的变性纤维蛋白-MTX的水解进行得较慢。溶解的纤维蛋白-MTX降解产物对单层培养的HeLa细胞生长有强烈的抑制作用，表明化疗活性MTX从其纤维蛋白衍生物中释放出来。
