Mizuno K, Furuhashi Y, Maeda O, Iwata M, Misawa T, Kawai M, Kano T, Tomoda Y
Department of Obstetrics and Gynecology, Nagoya University School of Medicine, Japan.
Cancer Chemother Pharmacol. 1990;26(5):333-9. doi: 10.1007/BF02897288.
We prepared Adriamycin-resistant cancer cells by exposing an ovarian serous cystadenocarcinoma cell line to the drug. The resistant cells also showed cross-resistance to a wide variety of other compounds, including vincristine, vinblastine, actinomycin D, daunorubicin, mitomycin C and carboquone. Against vincristine, the cells showed a greater than 5,000-fold increase in resistance, far surpassing their resistance to the selection drug. The resistant cells displayed a decrease in intracellular Adriamycin content and an increase in the mRNA of the mdr-1 gene coding for P-glycoprotein, with no amplification of the DNA. In revertant cells, resistance to Adriamycin was lost, but that to mitomycin C was maintained. Adriamycin resistance was partially overcome by the addition of verapamil or cyclosporin A, but cross-resistance to mitomycin C was not influenced at all. These results strongly suggest that the resistance to mitomycin C observed in our Adriamycin-resistant cells was due to some other mechanism than that causing multidrug resistance.
我们通过将一种卵巢浆液性囊腺癌细胞系暴露于阿霉素来制备阿霉素耐药癌细胞。这些耐药细胞还对多种其他化合物表现出交叉耐药性，包括长春新碱、长春花碱、放线菌素D、柔红霉素、丝裂霉素C和卡波醌。对于长春新碱，这些细胞的耐药性增加了5000倍以上，远远超过了它们对筛选药物的耐药性。耐药细胞的细胞内阿霉素含量降低，编码P-糖蛋白的mdr-1基因的mRNA增加，而DNA没有扩增。在回复细胞中，对阿霉素的耐药性丧失，但对丝裂霉素C的耐药性仍然存在。加入维拉帕米或环孢素A可部分克服对阿霉素的耐药性，但对丝裂霉素C的交叉耐药性完全不受影响。这些结果有力地表明，我们的阿霉素耐药细胞中观察到的对丝裂霉素C的耐药性是由导致多药耐药性的其他机制引起的。
