Pourtier-Manzanedo A, Boesch D, Loor F
Laboratoire d'Immunologie, Université Louis Pasteur Strasbourg, Illkirch, France.
Anticancer Drugs. 1991 Jun;2(3):279-83. doi: 10.1097/00001813-199106000-00010.
Cyclosporin A (CsA) and FK-506 have similar immunosuppressive activity profiles and cyclophilin-like intracellular targets. Since CsA can reverse the multidrug resistance of tumor cells showing P-glycoprotein-mediated drug efflux, the possible resistance-modulating activity of FK-506 was evaluated in vitro with multidrug-resistant P388 cells and their sensitive parental controls. Higher concentrations of FK-506 than CsA were needed to achieve a similar degree of chemosensitization, suggesting that FK-506 might interact less efficiently than CsA with the P-glycoprotein expressed in multidrug-resistant tumor cells. However, FK-506 was active on a broader range of concentrations than CsA, particularly because of direct cytostatic effects of CsA which appeared at concentrations only slightly higher than those required to show a significant resistance-modulating activity.
环孢素A（CsA）和FK-506具有相似的免疫抑制活性谱和类亲环蛋白的细胞内靶点。由于CsA可以逆转表现出P-糖蛋白介导的药物外排的肿瘤细胞的多药耐药性，因此在体外使用多药耐药的P388细胞及其敏感的亲本对照评估了FK-506可能的耐药调节活性。与CsA相比，需要更高浓度的FK-506才能达到相似程度的化学增敏作用，这表明FK-506与多药耐药肿瘤细胞中表达的P-糖蛋白的相互作用效率可能低于CsA。然而，FK-506在比CsA更宽的浓度范围内具有活性，特别是因为CsA的直接细胞抑制作用出现在仅略高于显示出显著耐药调节活性所需浓度的浓度下。
