Tsuruo T
Gan To Kagaku Ryoho. 1985 Sep;12(9):1715-25.
Acquired multidrug resistance as well as innate drug resistance are directly related to ineffectiveness and failure of the cancer chemotherapy. The mechanisms of such resistance, especially those of innate resistance, have not been fully elucidated. Drug resistant tumor cells, however, usually bear biochemical changes which are related to resistance mechanisms. New modalities with high selectivity against resistant cells could, therefore, be possible if we could target these biochemical changes. Vincristine (VCR)-and adriamycin (ADM)-resistant tumor cells (pleiotropic drug resistant cells) usually show an enhanced outward transport of these antitumor agents, and they express unique glycoproteins in the plasma membrane. By targeting for these biochemical changes characteristic to the resistant tumor cells, we establish new modality which shows high selectivity against drug resistant tumor cells. In this review, I will describe genetic origin of drug resistance, biochemical mechanisms of drug resistance and reversal of drug resistance in tumor cells. The modality to utilize calcium channel blockers which inhibit the enhanced outward transport of VCR and ADM from resistant tumor cells will be reviewed.
获得性多药耐药以及固有耐药都与癌症化疗的无效性和失败直接相关。这种耐药的机制，尤其是固有耐药的机制，尚未完全阐明。然而，耐药肿瘤细胞通常会发生与耐药机制相关的生化变化。因此，如果我们能够针对这些生化变化，就有可能开发出对耐药细胞具有高选择性的新方法。长春新碱（VCR）和阿霉素（ADM）耐药的肿瘤细胞（多药耐药细胞）通常表现出这些抗肿瘤药物向外转运增强，并且它们在质膜中表达独特的糖蛋白。通过针对耐药肿瘤细胞特有的这些生化变化，我们建立了一种对耐药肿瘤细胞具有高选择性的新方法。在这篇综述中，我将描述耐药的遗传起源、耐药的生化机制以及肿瘤细胞中耐药的逆转。将对利用钙通道阻滞剂抑制VCR和ADM从耐药肿瘤细胞向外增强转运的方法进行综述。
