Didier A, Tiberghien F, Wenger R, Loor F
Laboratoire d'Immunologie, Strasbourg 1 University, Illkirch, France.
Anticancer Drugs. 1996 May;7(3):257-65. doi: 10.1097/00001813-199605000-00004.
The P-glycoprotein (P-gp) molecules which are expressed on multidrug-resistant (MDR) tumor cells efflux a variety of anti-cancer drugs, such as doxorubicin. Though first described as an inhibitor of P-gp function, cyclosporin A (CsA) was more recently shown to behave as a substrate of the P-gp pump. The retention of [3H]CsA was reduced in MDR cells of the human leukemic CEM cell subline, in comparison with the drug-sensitive parental (Par) subline. MDR-CEM cell treatment by the P-gp blockers restored the [3H]CsA retention to the control Par-CEM cell levels. Using a novel fluorescent CsA derivative, [N-epsilon-(4-nitrobenzofurazan-7-yL)-D-Lys8] cyclosporin (NBDL-CsA), we now show that MDR cells can be distinguished from Par cells both at the cell population level (in microculture) and at the single cell level (by use of flow cytometry).
多药耐药（MDR）肿瘤细胞上表达的P-糖蛋白（P-gp）分子会排出多种抗癌药物，如阿霉素。虽然环孢素A（CsA）最初被描述为P-gp功能的抑制剂，但最近发现它也是P-gp泵的底物。与药物敏感的亲代（Par）细胞系相比，人白血病CEM细胞亚系的MDR细胞中[3H]CsA的保留量减少。用P-gp阻滞剂处理MDR-CEM细胞可使[3H]CsA的保留量恢复到对照Par-CEM细胞的水平。使用一种新型荧光CsA衍生物[N-ε-（4-硝基苯并呋喃唑-7-基）-D-赖氨酸8]环孢素（NBDL-CsA），我们现在表明，在细胞群体水平（微培养）和单细胞水平（通过流式细胞术）都可以区分MDR细胞和Par细胞。
