Hotta T, Tanimura H, Yamaue H, Iwahashi M, Tani M, Tsunoda T, Tamai M, Noguchi K, Mizobata S, Arii K, Terasawa H
Second Department of Surgery, Wakayama Medical School, 27-Shichibancho, Wakayama, 640, Japan.
J Surg Res. 1996 Nov;66(1):31-5. doi: 10.1006/jsre.1996.0368.
The resistance to doxorubicin (DOX) is mainly due to the effect of P-glycoprotein encoded by the multidrug resistance-1 (mdr1) gene. Tamoxifen (TAM) has been shown to circumvent multidrug resistance in P-glycoprotein-expressing cell lines. In the present study, we clarified the augmentation of DOX sensitivity by TAM using MTT assay in highly purified fresh human tumor cells obtained from 85 cancer patients. Moreover, the correlation between DOX sensitivity and P-glycoprotein expression was assessed by flow cytometry. DOX sensitivity was decreased in proportion to P-glycoprotein expression. The cytotoxicity of DOX was increased by TAM in tumor cells possessing low DOX sensitivity. Moreover, there was a significant correlation between the effect of TAM on cytotoxicity and P-glycoprotein expression. The concentration of DOX in tumor cells was increased in combined exposure of TAM with DOX, compared with the exposure of DOX alone. Thus, TAM might be able to circumvent DOX-resistance for treatment in cancer patients.
对阿霉素（DOX）的耐药性主要归因于多药耐药-1（mdr1）基因编码的P-糖蛋白的作用。已证实他莫昔芬（TAM）可克服表达P-糖蛋白的细胞系中的多药耐药性。在本研究中，我们使用MTT法，在从85例癌症患者获取的高度纯化的新鲜人肿瘤细胞中，阐明了TAM对DOX敏感性的增强作用。此外，通过流式细胞术评估了DOX敏感性与P-糖蛋白表达之间的相关性。DOX敏感性与P-糖蛋白表达成比例降低。在DOX敏感性低的肿瘤细胞中，TAM增加了DOX的细胞毒性。此外，TAM对细胞毒性的作用与P-糖蛋白表达之间存在显著相关性。与单独暴露于DOX相比，TAM与DOX联合暴露时肿瘤细胞中DOX的浓度增加。因此，TAM可能能够克服癌症患者治疗中的DOX耐药性。
