DIFFERENTIAL MODULATION OF DOXORUBICIN TOXICITY TO MULTIDRUG AND INTRINSICALLY DRUG-RESISTANT CELL-LINES BY ANTIESTROGENS AND THEIR MAJOR METABOLITES
DIFFERENTIAL MODULATION OF DOXORUBICIN TOXICITY TO MULTIDRUG AND INTRINSICALLY DRUG-RESISTANT CELL-LINES BY ANTIESTROGENS AND THEIR MAJOR METABOLITES
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DOI：
10.1038/bjc.1993.224
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发表时间：
1993-06-01
影响因子：
8.8
通讯作者：
CARMICHAEL, J
中科院分区：
文献类型：
--
作者：
KIRK, J;HOULBROOK, S;CARMICHAEL, J
使用人乳腺癌、肺癌和中国仓鼠卵巢细胞系，比较了抗雌激素他莫昔芬、托瑞米芬及其4-羟基和N-去甲基代谢物改变阿霉素（dox）对固有耐药和多药耐药细胞系毒性的能力。抗雌激素显着增强多药耐药，P-糖蛋白阳性细胞系的毒性，但不影响毒性的内在耐药，P-糖蛋白阴性细胞。在临床上可达到的抗雌激素浓度下观察到改变。因此，托瑞米芬和他莫昔芬似乎是在选定的P-糖蛋白阳性肿瘤患者体内研究作为MDR调节剂的良好候选者。
The ability of the anti-oestrogens tamoxifen, toremifene and their 4-hydroxy and N-desmethyl metabolites to modify doxorubicin (dox) toxicity to intrinsically resistant and multidrug resistant cell lines was compared, using human breast and lung cancer, and Chinese hamster ovary cell lines. The anti-oestrogens significantly enhanced dox toxicity to multidrug resistant, P-glycoprotein-positive cell lines, but did not affect toxicity to intrinsically resistant, P-glycoprotein-negative cells. Modification was observed at clinically achievable anti-oestrogen concentrations. Toremifene and tamoxifen would therefore appear to be good candidates for in vivo studies as MDR modulating agents in selected patients with P-glycoprotein-positive tumours.