Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26).
Atypical multiple drug resistance in a human leukemic cell line selected for resistance to teniposide (VM-26).
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发表时间：
1987-03
期刊：
影响因子：
11.2
通讯作者：
M. Danks;J. Yalowich;W. T. Beck
中科院分区：
文献类型：
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作者：
M. Danks;J. Yalowich;W. T. Beck
暴露于单一药剂后对许多天然产物药物的细胞毒性作用的抗性是常见的观察结果。包括在“经典的”多重耐药表型中的药物类别是阿托伐他汀生物碱、蒽环类、表鬼臼毒素和抗生素。我们在此报告了一种具有“非典型”多重耐药的人白血病细胞系（CEM/VM-1）的特征：尽管对依托泊苷、蒽环类药物、米托蒽醌和4 '-[（9-吖啶基）氨基]甲磺酰-间-茴香胺（mAMSA）具有耐药性和交叉耐药性，但这些细胞仍保持着对阿托伐他汀生物碱的敏感性。此外，尽管该细胞系对依托泊苷（VP-16）的细胞毒性作用具有约40倍的交叉耐药性，但其在[3 H]VP-16的细胞药理学方面与药物敏感性CEM细胞相似，如通过零时间结合、初始流入速率、稳态药物浓度和单向流出所确定的。我们的研究表明，CEM/VM-1细胞对表鬼臼毒素的耐药性是由于药物与其细胞靶点之间的相互作用改变，其机制与“经典”多药耐药表型相关的药物细胞浓度降低无关。
Resistance to the cytotoxic effects of many natural product drugs after exposure to a single agent is a common observation. The classes of drugs included in the "classic" multiple drug resistance phenotype are Vinca alkaloids, anthracyclines, epipodophyllotoxins, and antibiotics. We report here the characterization of a human leukemic cell line (CEM/VM-1) with "atypical" multiple drug resistance: despite resistance and cross-resistance to etoposide, anthracyclines, mitoxantrone, and 4'-[(9-acridinyl)amino]methanesulphon-m-anisidide (mAMSA), these cells retain sensitivity to the Vinca alkaloids. Further, even though this cell line is approximately equal to 40-fold cross-resistant to the cytotoxic effect of etoposide (VP-16), it is similar to drug-sensitive CEM cells in the cellular pharmacology of [3H]VP-16 as determined by zero time binding, initial influx rate, steady state drug concentration, and unidirectional efflux. Our studies suggest that the resistance of CEM/VM-1 cells to epipodophyllotoxins is due to an altered interaction between drug and its cellular target(s) by a mechanism unrelated to the decreased cellular concentration of drug associated with the "classic" multiple drug resistance phenotype.