Laboratoire Chrono Environnement UMR CNRS 6249, Université de Bourgogne Franche-Comté, 16 route de Gray, 25030, Besançon, Cedex, France.
Department of Physics of Biological Systems, Institute of Physics of the National Academy of Sciences of Ukraine, Prospect Nauky 46, 03028, Kyiv, Ukraine.
Sci Rep. 2019 Apr 4;9(1):5627. doi: 10.1038/s41598-019-41903-w.
The composition of the plasma membrane of malignant cells is thought to influence the cellular uptake of cisplatin and to take part in developing resistance to this widespread anti-cancer drug. In this work we study the permeation of cisplatin through the model membranes of normal and cancer cells using molecular dynamics simulations. A special attention is paid to lipid asymmetry and cholesterol content of the membranes. The loss of lipid asymmetry, which is common for cancer cells, leads to a decrease in their permeability to cisplatin by one order of magnitude in comparison to the membranes of normal cells. The change in the cholesterol molar ratio from 0% to 33% also decreases the permeability of the membrane by approximately one order of magnitude. The permeability of pure DOPC membrane is 5-6 orders of magnitude higher than one of the membranes with realistic lipid composition, which makes it as an inadequate model for the studies of drug permeability.
人们认为恶性细胞的质膜组成会影响顺铂的细胞摄取，并参与对这种广泛使用的抗癌药物的耐药性的形成。在这项工作中，我们使用分子动力学模拟研究了顺铂通过正常细胞和癌细胞模型膜的渗透。特别关注了膜的脂质不对称性和胆固醇含量。对于癌细胞来说，脂质不对称性的丧失会导致其对顺铂的通透性比正常细胞的膜下降一个数量级。胆固醇摩尔比从 0%变化到 33%也会使膜的通透性大约下降一个数量级。纯 DOPC 膜的通透性比具有实际脂质组成的膜高 5-6 个数量级，这使得它作为药物通透性研究的模型是不充分的。
