Jachez B, Cianfriglia M, Loor F
Preclinical Research, Sandoz Pharma Ltd, Basel, Switzerland.
Anticancer Drugs. 1994 Dec;5(6):655-65. doi: 10.1097/00001813-199412000-00008.
Three monoclonal antibodies (mAb), MRK16, MM4.17 and MC57, directed against distinct epitopes on the external domain of human P-glycoprotein (Pgp), were used to follow its expression on multidrug resistant (MDR)-cells. The linear MM4.17 epitope and conformational MRK16 epitope showed a 4-fold higher expression at 37 degrees C than at 4 degrees C, while the detection of the conformational MC57 epitope did not change. Inhibition of Pgp function, by a short pretreatment of the MDR-cells with resistance-modulating agents (RMA), such as SDZ PSC 833 and SDZ 280-446, could not be related to depletion of Pgp from the cell surface, since their expression of the MM4.17 and MRK16 epitopes was found unchanged. However, a substantially higher expression of MC57 epitopes was found on RMA-treated cells than on untreated ones. Since this effect correlated to the strength of different RMA in reversing the MDR phenotype, MC57 epitopes might be more efficiently expressed on inactivate(d) forms of the Pgp molecules, suggesting that RMA might inhibit Pgp function by disturbing the conformation of individual Pgp molecules, their topographical distribution or polymerization status in the membrane.
三种针对人P-糖蛋白（Pgp）外结构域不同表位的单克隆抗体（mAb），即MRK16、MM4.17和MC57，被用于追踪其在多药耐药（MDR）细胞上的表达情况。线性的MM4.17表位和构象性的MRK16表位在37℃时的表达比在4℃时高4倍，而构象性MC57表位的检测结果没有变化。用耐药调节剂（RMA）如SDZ PSC 833和SDZ 280 - 446对MDR细胞进行短期预处理来抑制Pgp功能，这与细胞表面Pgp的消耗无关，因为发现它们的MM4.17和MRK16表位的表达没有改变。然而，在经RMA处理的细胞上发现MC57表位的表达明显高于未处理的细胞。由于这种效应与不同RMA逆转MDR表型的强度相关，MC57表位可能在Pgp分子的失活形式上更有效地表达，这表明RMA可能通过干扰单个Pgp分子的构象、其拓扑分布或膜中的聚合状态来抑制Pgp功能。
