SELECTIVE REVERSAL OF VINBLASTINE RESISTANCE IN MULTIDRUG-RESISTANT CELL-LINES BY TAMOXIFEN, TOREMIFENE AND THEIR METABOLITES
SELECTIVE REVERSAL OF VINBLASTINE RESISTANCE IN MULTIDRUG-RESISTANT CELL-LINES BY TAMOXIFEN, TOREMIFENE AND THEIR METABOLITES
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DOI：
10.1016/s0959-8049(05)80306-5
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发表时间：
1993-01-01
影响因子：
8.4
通讯作者：
CARMICHAEL, J
中科院分区：
文献类型：
--
作者：
KIRK, J;HOULBROOK, S;CARMICHAEL, J
在这项研究中，我们描述了他莫昔芬，托瑞米芬及其4-羟基和N-去甲基代谢产物对一系列药物对人乳腺癌和肺癌以及中国仓鼠卵巢细胞系的毒性的影响，使用基于四氮唑的半自动比色法测定。长春碱耐药在多药耐药基因转染的肺癌细胞系（S1/1.1）中被完全消除，表明P-糖蛋白介导的多药耐药可以被抗雌激素完全逆转。在他莫昔芬、托瑞米芬及其代谢产物存在下，也观察到长春碱对表达P-糖蛋白的高度多药耐药（MCF-7Adr）细胞的毒性显著增强（14- 39倍），而间安吖啶、顺铂和美法仑的毒性不受影响。
In this study we describe the effects of tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites on the toxicity of a range of drugs to human breast and lung cancer and to Chinese hamster ovary cell lines, determined using a tetrazolium-based semi-automated colorimetric assay. Vinblastine resistance was completely abolished in an mdr1-transfected lung cancer cell line (S1/1.1), indicating that P-glycoprotein-mediated multidrug resistance can be fully reversed by anti-oestrogens. A substantial (14- to 39-fold) enhancement of vinblastine toxicity to highly multidrug-resistant (MCF-7Adr) cells expressing P-glycoprotein was also observed in the presence of tamoxifen, toremifene and their metabolites, while m-amsacrine, cisplatin and melphalan toxicity was unaffected.