迁移他汀对多药耐药性的抑制作用。

Suppression of multidrug resistance by migrastatin.

作者信息

Takemoto Yasushi, Tashiro Etsu, Imoto Masaya

机构信息

Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.

出版信息

J Antibiot (Tokyo). 2006 Jul;59(7):435-8. doi: 10.1038/ja.2006.62.

DOI:10.1038/ja.2006.62

PMID:17025021

Abstract

Migrastatin (MGS) is a Streptomyces metabolite that inhibits cancer cell migration. In this study, we found that MGS also enhanced the cytotoxicity of vinblastine, vincristine, and taxol in P-glycoprotein-overexpressing VJ-300 cells and P388/VCR cells. Furthermore, MGS increased the intracellular concentration of labeled vinblastine, vincristine, and taxol in both VJ-300 cells and P388/VCR cells. P-glycoprotein was photolabeled with [3H]azidopine, but this photolabeling was significantly inhibited in the presence of MGS. These results indicated that MGS directly interacts with and inhibits P-glycoprotein, thereby sensitizing drug-resistant cells to anticancer drugs.

摘要

迁移抑制素（MGS）是一种链霉菌代谢产物，可抑制癌细胞迁移。在本研究中，我们发现MGS还增强了长春碱、长春新碱和紫杉醇对过表达P-糖蛋白的VJ-300细胞和P388/VCR细胞的细胞毒性。此外，MGS增加了VJ-300细胞和P388/VCR细胞中标记的长春碱、长春新碱和紫杉醇的细胞内浓度。P-糖蛋白用[3H]叠氮平进行光标记，但在MGS存在下这种光标记受到显著抑制。这些结果表明，MGS直接与P-糖蛋白相互作用并抑制它，从而使耐药细胞对抗癌药物敏感。