Burns C P, Haugstad B N, Mossman C J, North J A, Ingraham L M
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242.
Lipids. 1988 May;23(5):393-7. doi: 10.1007/BF02535508.
We have studied the effect of membrane structural alteration on the cellular association of the anticancer drug mitoxantrone whose uptake is not carrier-mediated. Membrane fatty acids of L1210 cells were modified by incubating the cells with the highly unsaturated docosahexaenoic acid (22:6), which results in isolated plasma membranes with 37% of the fatty acids as 22:6, or with the monounsaturated oleic acid (18:1), which results in 58% of the fatty acids as 18:1. The rate of uptake by 22:6-enriched cells during the first min was 62% greater than by those enriched with 18:1. The higher rate was recorded at 0.5-16 microM, pH 6.6-7.6 and temperatures 10-40 C. The difference in cell-associated drug apparently was not due simply to a change in mitoxantrone solubility as measured by partitioning of the drug in lipophilic-hydrophilic systems containing lipids from the fatty-acid altered cells. We conclude that the type of fatty acids contained in L1210 cell membranes can affect the cell association of mitoxantrone. This effect could be on transmembrane flux or be due to differences in binding of the drug to intracellular structures.
我们研究了膜结构改变对抗癌药物米托蒽醌细胞摄取的影响，米托蒽醌的摄取不是载体介导的。通过将L1210细胞与高度不饱和的二十二碳六烯酸（22:6）孵育来修饰其膜脂肪酸，这会导致分离的质膜中37%的脂肪酸为22:6，或者与单不饱和油酸（18:1）孵育，这会使58%的脂肪酸为18:1。在最初的1分钟内，富含22:6的细胞的摄取速率比富含18:1的细胞高62%。在0.5 - 16 microM、pH 6.6 - 7.6和温度10 - 40℃时记录到较高的摄取速率。细胞相关药物的差异显然不仅仅是由于米托蒽醌溶解度的变化，这是通过将药物在含有来自脂肪酸改变细胞的脂质的亲脂 - 亲水系统中的分配来测量的。我们得出结论，L1210细胞膜中所含脂肪酸的类型会影响米托蒽醌与细胞的结合。这种影响可能作用于跨膜通量，或者是由于药物与细胞内结构结合的差异。
