Ryffel B, Woerly G, Rodriguez C, Foxwell B M
Sandoz Pharma Ltd., Basel, Switzerland.
J Recept Res. 1991;11(1-4):675-86. doi: 10.3109/10799899109066435.
The immunosuppressive agent cyclosporine A (CSA) has been shown to reverse multidrug resistance (MDR) in malignant cells. In the present study, a 3H-cyclosporine diazirine analogue (3H-PL-CS) was used to photolabel viable MDR cells. The 170 kDa membrane P-glycoprotein, which functions as a drug efflux pump, was strongly labeled. The binding of 3H-cyclosporine diazirine analogue to P-glycoprotein was competable by excess cyclosporine A and by the nonimmunosuppressive cyclosporine H. These results suggest that cyclosporine reverses the MDR phenotype by binding directly to P-glycoprotein and that this binding is not dependent on the immunosuppressive potential of the cyclosporine derivative. The identification of P-glycoprotein as a cyclosporine binding protein has obvious implications for cancer chemotherapy.
免疫抑制剂环孢素A（CSA）已被证明可逆转恶性细胞中的多药耐药性（MDR）。在本研究中，一种3H-环孢素重氮丙啶类似物（3H-PL-CS）被用于对存活的MDR细胞进行光标记。作为药物外排泵发挥作用的170 kDa膜P-糖蛋白被强烈标记。3H-环孢素重氮丙啶类似物与P-糖蛋白的结合可被过量的环孢素A和非免疫抑制性的环孢素H竞争。这些结果表明，环孢素通过直接与P-糖蛋白结合来逆转MDR表型，并且这种结合不依赖于环孢素衍生物的免疫抑制潜力。将P-糖蛋白鉴定为环孢素结合蛋白对癌症化疗具有明显的意义。
