Lison D, Knoops B, Collette C, Lauwerys R
Unité de Toxicologie Industrielle et Médecine, Faculté de Médecine, Université Catholique de Louvain, Bruxelles, Belgium.
Biochem Pharmacol. 1989 Jul 1;38(13):2107-12. doi: 10.1016/0006-2952(89)90064-6.
Urokinase-type plasminogen activator, a neutral proteinase, seems to play a central role in the degradation of the extracellular matrix that accompanies a number of biological phenomena including inflammatory reactions and neoplasia. The effect of auranofin and retinoic acid on the plasminogen activator activity expressed by two cell types, i.e. murine macrophages and Lewis lung carcinoma cells, has been investigated. Low concentrations of both drugs (10(-6)-10(-7) M) can inhibit in vitro the induction of plasminogen activator in macrophages stimulated by phorbol 12-myristate 13-acetate. This action occurs rapidly (15 min), is irreversible and is independent of a global cytotoxic effect. Auranofin and retinoic acid remain without effect in macrophages when added after stimulation by the phorbol ester. Both drugs are thus potent inhibitors of the induction of plasminogen activator activity in macrophages, possibly through an interaction with the protein kinase C system. The plasminogen activator activity of Lewis lung carcinoma cells, which is apparently not dependent on a protein kinase C pathway, is not influenced by auranofin or retinoic acid. These observations may contribute to explain: (1) the activity of auranofin and retinoic acid in rheumatoid arthritis, and (2) the antitumor promoting activity of retinoic acid. It would be relevant to assess whether auranofin may exhibit, like retinoic acid, an antitumor-promoting activity.
尿激酶型纤溶酶原激活剂是一种中性蛋白酶，似乎在细胞外基质降解过程中发挥核心作用，而这种降解伴随着包括炎症反应和肿瘤形成在内的多种生物学现象。研究了金诺芬和视黄酸对两种细胞类型（即小鼠巨噬细胞和刘易斯肺癌细胞）表达的纤溶酶原激活剂活性的影响。两种药物的低浓度（10⁻⁶ - 10⁻⁷ M）均可在体外抑制佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯刺激的巨噬细胞中纤溶酶原激活剂的诱导。这种作用迅速发生（15分钟），是不可逆的，且与整体细胞毒性作用无关。在佛波醇酯刺激后添加金诺芬和视黄酸时，它们对巨噬细胞没有影响。因此，这两种药物可能通过与蛋白激酶C系统相互作用，成为巨噬细胞中纤溶酶原激活剂活性诱导的有效抑制剂。刘易斯肺癌细胞的纤溶酶原激活剂活性显然不依赖于蛋白激酶C途径，不受金诺芬或视黄酸的影响。这些观察结果可能有助于解释：（1）金诺芬和视黄酸在类风湿性关节炎中的活性，以及（2）视黄酸的抗肿瘤促进活性。评估金诺芬是否可能像视黄酸一样具有抗肿瘤促进活性将是有意义的。
