作用于基质金属蛋白酶的抗生素

Antibiotics acting on matrix metalloproteinases

基质金属蛋白酶 (matrix metalloproteinases,MMPs)是在与组织重塑有关的生理过程和以细胞外基质过度破坏为主要特征的病理过程中起重要作用的一类锌离子依赖性内肽酶。近些年来 ,MMPs在恶性肿瘤侵袭、生长和转移过程中的作用日益受到重视。我们以在肿瘤细胞破坏和穿过基底膜发生侵袭和转移过程中起重要作用的 MMPs家族成员 IV型胶原酶为研究对象 ,利用抗 IV型胶原酶单克隆抗体 3D6为工具 ,采用间接 EL ISA方法研究了四种抗生素对 IV型胶原酶或能够分泌 IV型胶原酶的 PG细胞的作用。结果表明 ,geldanamycin和博安霉素均能竞争性地抑制 3D6与 IV型胶原酶或 PG细胞的结合 ,说明其作用于 IV型胶原酶并可能对其活性产生抑制作用 ;而米诺环素在实验浓度下仅对 3D6和 PG细胞的结合表现出抑制作用。另外 ,我们发现地红霉素亦能够抑制单抗 3D6与 IV型胶原酶或 PG细胞的结合。结果表明 ,这四种抗生素可能作用于基质金属蛋白酶。

Matrix metalloproteinases are a family of Zn 2+ dependent endopeptidases which play important roles both in the physiological processes related with tissue remodeling and in the pathological destruction characterized with excessive turnover of extracellular matrix. Recently, the roles of MMPs in tumor invasion, metastasis and angiogenesis were verified. Using type Ⅳ collagenase, which belongs to one subgroup of MMPs as a target and anti type Ⅳ collagenase monoclonal antibody 3D6 as a tool, we studied the effect of several antibiotics on the binding of 3D6 to type Ⅳ collagenase or PG cells which are highly immunoreactive with 3D6 by indirected ELISA method. As a result,geldanamycin and boanmycin showed competively inhibitory effect on the binding of 3D6 to both type Ⅳ collagenase and PG cells. Minocycline inhibited the binding of 3D6 to PG cells, however it didn′t show effect on the binding of 3D6 to type Ⅳ collagenase. Another antibiotic, dirithromycin also displayed inhibitory effects on the binding of 3D6 to type Ⅳ collagenase and PG cells. Results indicated that these four antibiotics acted on matrix metallopropteinases.