Dodion P, Sanders C, Rombaut W, Mattelaer M A, Rozencweig M, Stryckmans P, Kenis Y
Service de Médecine, Institut Jules Bordet, Brussels, Belgium.
Eur J Cancer Clin Oncol. 1987 Dec;23(12):1909-14. doi: 10.1016/0277-5379(87)90058-7.
The cytotoxic effect of daunorubicin, carminomycin, idarubicin and the major metabolite of idarubicin in man, 4-demethoxydaunorubicinol, was investigated in a human normal progenitor myeloid stem cell assay and in a human tumor stem cell assay. Against normal myeloid progenitor cells, idarubicin and carminomycin were equally potent; both agents were significantly (P less than or equal to 0.01) more potent than daunorubicin. Idarubicin was approx. 2.5 times more potent than 4-demethoxydaunorubicinol. Against malignant tumor cells, 50% cell kill after exposure to idarubicin was observed in four out 24 samples; this inhibition occurred at a drug concentration of 0.1 micrograms/ml. Two of the samples sensitive to idarubicin were also sensitive to 4-demethoxydaunorubicinol at a concentration of 0.1 micrograms/ml. Overall, idarubicin was active against two out of six ovarian carcinomas and against one out of three breast carcinomas. Our data confirm that 4-demethoxydaunorubicinol may play a role in the biological activity of idarubicin.
在人正常祖髓样干细胞试验和人肿瘤干细胞试验中，研究了柔红霉素、卡米诺霉素、伊达比星以及伊达比星在人体内的主要代谢产物4-去甲氧基柔红霉素醇的细胞毒性作用。对于正常髓样祖细胞，伊达比星和卡米诺霉素的效力相当；这两种药物均比柔红霉素的效力显著更强（P≤0.01）。伊达比星的效力约为4-去甲氧基柔红霉素醇的2.5倍。对于恶性肿瘤细胞，在24个样本中有4个样本在暴露于伊达比星后观察到50%的细胞杀伤；这种抑制作用在药物浓度为0.1微克/毫升时出现。对伊达比星敏感的两个样本对浓度为0.1微克/毫升的4-去甲氧基柔红霉素醇也敏感。总体而言，伊达比星对6例卵巢癌中的2例以及3例乳腺癌中的1例有活性。我们的数据证实4-去甲氧基柔红霉素醇可能在伊达比星的生物活性中起作用。
