Nagasawa K, Ohnishi N, Yokoyama T
Department of Hospital Pharmacy, Faculty of Pharmaceutical Sciences, Kyoto Pharmaceutical University.
Jpn J Cancer Res. 1997 Aug;88(8):750-9. doi: 10.1111/j.1349-7006.1997.tb00447.x.
Transport mechanisms of idarubicin (IDA) in HL60 cells, as leukemia cells, and human mononuclear cells (MNCs), as normal cells, were investigated, and compared with those of its analogs. The uptake of IDA by both cell types was temperature- and concentration-dependent, was inhibited competitively by daunorubicin (DNR) and noncompetitively by adriamycin (ADR), and was stimulated by preloading of the cells with DNR and ADR, indicating the partial involvement of a carrier-mediated mechanism. On pretreatment of the cells with 2,4-dinitrophenol, IDA uptake by HL60 cells increased, but that by MNCs decreased, suggesting that IDA was partially taken up into HL60 cells via an energy-independent carrier system, and into MNCs via an energy-dependent one. We speculated that in HL60 cells the carrier concerned with IDA uptake was common to DNR and ADR, and that the binding site of IDA on the carrier was the same as that for DNR, but not that for ADR, while in MNCs the carrier system consisted of, at least in part, a carrier for DNR uptake and one for ADR uptake, and the binding site of IDA was identical to that for DNR in the former, but different from that for ADR in the latter. It appeared that the uptake of IDA was greater than those of pirarubicin, DNR and ADR in both HL60 cells and MNCs, and that IDA was incorporated into MNCs more efficiently than into HL60 cells because of the higher uptake efficacy of the carrier(s).
研究了白血病细胞HL60细胞和正常细胞人单核细胞（MNCs）中伊达比星（IDA）的转运机制，并将其与其类似物的转运机制进行了比较。两种细胞类型对IDA的摄取均呈温度和浓度依赖性，受柔红霉素（DNR）竞争性抑制，受阿霉素（ADR）非竞争性抑制，并且通过用DNR和ADR预加载细胞可刺激摄取，表明部分涉及载体介导的机制。用2,4-二硝基苯酚预处理细胞后，HL60细胞对IDA的摄取增加，但MNCs对IDA的摄取减少，这表明IDA部分通过能量非依赖性载体系统进入HL60细胞，部分通过能量依赖性载体系统进入MNCs。我们推测，在HL60细胞中，与IDA摄取相关的载体对DNR和ADR是通用的，并且IDA在载体上的结合位点与DNR相同，但与ADR不同，而在MNCs中，载体系统至少部分由用于DNR摄取的载体和用于ADR摄取的载体组成，并且IDA的结合位点在前者中与DNR相同，但在后者中与ADR不同。似乎在HL60细胞和MNCs中，IDA的摄取均大于吡柔比星、DNR和ADR的摄取，并且由于载体的摄取效率较高，IDA进入MNCs的效率高于进入HL60细胞的效率。
