Mechanism of resistance to anthracyclines and vinca alkaloids.
Mechanism of resistance to anthracyclines and vinca alkaloids.
复制标题
对蒽环类药物和长春花生物碱的耐药机制。
DOI：
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发表时间：
1983
期刊：
影响因子：
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通讯作者：
A. D. Di Marco
中科院分区：
文献类型：
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作者：
K. Danø;T. Skovsgaard;N. Nissen;E. Friche;A. D. Di Marco
在对这些药物产生获得性耐药的实验性肿瘤中，蒽环类药物和长春花碱之间发生交叉耐药是常见的。到目前为止，还没有迹象表明这种现象是由于这两组药物共同的细胞内作用机制造成的。在几乎所有已报道的研究中，获得性实验耐药和交叉耐药与这两种药物的细胞积累减少有关，尽管也涉及其他因素。在Ehrlich腹水肿瘤中，一些稳态条件下的研究结果表明，药物积聚的减少依赖于主动向外转运药物的细胞机制，这在蒽环类药物和长春花碱中是常见的，但向内转运和细胞内结合能力的变化也起到了作用。在P388白血病的耐药性和交叉耐药性方面也有类似的发现。本文讨论了通过抑制药物向外转运来对抗动物肿瘤获得性实验耐药的最新结果，以及不同的蒽环类化合物对柔红霉素在耐药细胞中积累的影响的研究。
Occurrence of cross-resistance between anthracyclines and vinca alkaloids is the rule in experimental tumors with acquired resistance to these drugs. So far, there is no indication that this phenomenon is due to an intracellular mechanism of action common to the two groups of drugs. In nearly all reported studies, acquired experimental resistance and cross-resistance are related to a decreased cellular accumulation of both types of drugs, although other factors also are involved. In Ehrlich ascites tumors, a number of findings at steady-state conditions indicate that the decreased accumulation is dependent on a cellular mechanism for active outward drug transport, which is common to anthracyclines and vinca alkaloids, but changes in inward transport and intracellular binding capacity also contribute. Similar findings have been reported for resistance and cross-resistance in P388 leukemia. Recent results with counteraction of acquired experimental resistance in animal tumors by inhibition of outward drug transport and studies on the effect of different anthracycline derivatives on accumulation of daunomycin in resistant cells are discussed.