Miyamoto Y, Maeda H
Department of Microbiology, Kumamoto University Medical School.
Jpn J Cancer Res. 1991 Mar;82(3):351-6. doi: 10.1111/j.1349-7006.1991.tb01853.x.
Multidrug-resistant CHRC5 cells were about 10-fold more resistant to the proteinaceous anticancer drug neocarzinostatin (NCS) and its nonprotein chromophore (NPC) than the parental AUXB1 cells. There was little difference in cell growth, glutathione content, or activities of several antioxidant enzymes between the two cell lines. The degree of intracellular incorporation and extracellular excretion of fluorescein isothiocyanate-labeled NCS by CHRC5 cells was similar to that of AUXB1 cells. On the other hand, 20 microM verapamil or 27 microM cepharanthine restored the susceptibility of CHRC5 cells to NCS and NPC to the level of AUXB1 cells. In addition, NPC was found to suppress the photolabeling of [3H]azidopine (a known P-glycoprotein-binding ligand) to plasma membranes of CHRC5 cells. All these findings favor the possibility that NPC was excreted via P-glycoprotein, which may contribute to the resistance of CHRC5 cells to NCS.
多药耐药的CHRC5细胞对蛋白质类抗癌药物新制癌菌素（NCS）及其非蛋白质发色团（NPC）的耐药性比亲代AUXB1细胞高约10倍。两种细胞系在细胞生长、谷胱甘肽含量或几种抗氧化酶的活性方面几乎没有差异。CHRC5细胞对异硫氰酸荧光素标记的NCS的细胞内摄取和细胞外排泄程度与AUXB1细胞相似。另一方面，20微摩尔的维拉帕米或27微摩尔的千金藤素可使CHRC5细胞对NCS和NPC的敏感性恢复到AUXB1细胞的水平。此外，发现NPC可抑制[3H]叠氮平（一种已知的P-糖蛋白结合配体）对CHRC5细胞质膜的光标记。所有这些发现都支持NPC通过P-糖蛋白排泄的可能性，这可能导致CHRC5细胞对NCS产生耐药性。
