Aouali Nasséra, Morjani Hamid, Trussardi Aurélie, Soma Emilienne, Giroux Bruno, Manfait Michel
Unité MéDIAN CNRS UMR6142, IFR53, UFR de Pharmacie, 51096 Reims cedex, France.
Int J Oncol. 2003 Oct;23(4):1195-201.
Previous studies have demonstrated that doxorubicin (DOX) encapsulated in polyisohexylcyano-acrylate nanospheres (NS-DOX) circumvented the resistance of breast cancer cells overexpressing P-glycoprotein (Pgp). Another protein is involved in multidrug resistance phenotype, the multidrug resistance associated protein (MRP1). We report that NS-DOX overcomes multidrug resistance in breast cancer cells overexpressing MRP1. Taking into account that anthracyclines are conjugated to or co-transported with glutathione by MRP1, these data suggest that probably due to ion pair formation (NS-DOX), MRP1 could not transport the anthracycline. Pgp is probably able to transport the ion pair drug complex and the mechanisms of drug resistance reversion in Pgp expressing cells need to be further elucidated.
先前的研究表明，包裹在聚异己基氰基丙烯酸酯纳米球（NS-DOX）中的阿霉素（DOX）可克服过表达P-糖蛋白（Pgp）的乳腺癌细胞的耐药性。另一种与多药耐药表型有关的蛋白是多药耐药相关蛋白（MRP1）。我们报告NS-DOX可克服过表达MRP1的乳腺癌细胞的多药耐药性。考虑到蒽环类药物可被MRP1与谷胱甘肽结合或共同转运，这些数据表明可能由于离子对形成（NS-DOX），MRP1无法转运蒽环类药物。Pgp可能能够转运离子对药物复合物，而在表达Pgp的细胞中逆转耐药性的机制需要进一步阐明。
