Mode of action of calcium antagonists which alter anthracycline resistance.
Mode of action of calcium antagonists which alter anthracycline resistance.
复制标题
改变蒽环类药物耐药性的钙拮抗剂的作用方式。
DOI：
10.1016/0006-2952(84)90533-1
复制
发表时间：
1984
影响因子：
5.8
通讯作者：
Wilberding,C
中科院分区：
文献类型：
--
作者：
Kessel,D;Wilberding,C
在可移植的肿瘤细胞系中，对几种天然产物（包括蒽环类药物、长春花生物碱和放线菌素D）的常见耐药模式涉及向外运输过程，该过程将药物积累限制在亚致死水平（1-5）。两种结构类型的钙拮抗剂可以抑制这种转运系统，并促进药物反应性：罂粟碱类似物，如维拉帕米和二氢嘧啶，如尼群地平（6-9）。本报告描述了上述两类钙拮抗剂的研究。这些数据表明维拉帕米是向外运输系统的底物，并通过向外运输的竞争促进蒽环类药物的积累。尼群地平不是这种向外运输系统的底物，可能通过“混沌性”机制起作用。
In transplantable tumor cell lines, a common mode of resistance to several natural products, including the anthracyclines, the Vinca alkaloids and actinomycin D, involves an outward transport process which limits drug accumulation to sub-lethal levels (1–5). This transport system can be inhibited, and drug responsiveness promoted, by calcium antagonists of two structural classes: papaverine analogs, e.g. verapamil, and dihydropyrimidines, e.g. nitrendipine (6–9). This report describes studies on the two classes of calcium antagonists named above. The data indicate that verapamil is a substrate for the outward transport system and promotes anthracycline accumulation via competition for exodus. Nitrendipine is not a substrate for this outward transport system and may act via a ‘chaotropic’ mechanism.