抗P-糖蛋白单克隆抗体MRK-16增强环孢素A对长春新碱耐药的逆转作用
Enhancement of reversing effect of cyclosporin A on vincristine resistance by anti-P-glycoprotein monoclonal antibody MRK-16.
作者信息
Naito M, Tsuge H, Kuroko C, Tomida A, Tsuruo T
机构信息
Institute of Applied Microbiology, University of Tokyo.
出版信息
Jpn J Cancer Res. 1993 May;84(5):489-92. doi: 10.1111/j.1349-7006.1993.tb00164.x.
The synergistic effect of MRK-16, a monoclonal antibody against P-glycoprotein, and cyclosporin A (CsA) on the modulation of vincristine resistance was studied by isobologram analysis in three different, highly multidrug-resistant tumor cells. In all cell lines, the synergistic effect was demonstrated at various concentrations of MRK-16 and CsA. While MRK-16 alone did not enhance the sensitivity of the moderately resistant KB-8-5 cells to vincristine, it increased two-fold the reversing effect of cyclosporin A at 1 microM, an achievable blood concentration. Since MRK-16 alone showed therapeutic effects against multidrug-resistant tumors, the combined use of MRK-16, CsA and antitumor agents should provide therapeutic benefits for the treatment of resistant tumors.
通过等效线图分析，在三种不同的、高度耐多药的肿瘤细胞中研究了抗P-糖蛋白单克隆抗体MRK-16与环孢素A（CsA）对长春新碱耐药性调节的协同作用。在所有细胞系中，在不同浓度的MRK-16和CsA下均显示出协同作用。虽然单独使用MRK-16不会增强中度耐药的KB-8-5细胞对长春新碱的敏感性，但在1 microM（可达到的血药浓度）时，它使环孢素A的逆转作用增加了两倍。由于单独使用MRK-16对耐多药肿瘤显示出治疗效果，因此联合使用MRK-16、CsA和抗肿瘤药物应为耐药肿瘤的治疗提供治疗益处。
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