Didier A, Wenger J, Loor F
Laboratoire d'Immunologie, Strasbourg 1 University, Illkirch, France.
Anticancer Drugs. 1995 Oct;6(5):669-80. doi: 10.1097/00001813-199510000-00006.
The P-glycoprotein (Pgp) molecules which are expressed on multidrug resistant (MDR) tumor cells can efflux a variety of cytostatics. In both normal and tumoral epitheliums, Pgp molecules are selectively expressed on the apical surface of the epithelial cells. Such a distribution seems to be responsible for the transcellular transport of Pgp substrates, including cyclosporin A (CsA), from the basal to the apical side. Some normal lymphoid cells also express small amounts of Pgp molecules, for as yet unknown functions. Nevertheless, the sensitivity of their mitogen-induced proliferation to cytostatics, including doxorubicin and CsA, could be increased by the Pgp blockers. Using isotopically-labeled CsA and tumoral lymphoid cell lines, we now show a higher CsA retention in Pgp-lacking parental ('Par') cells than in Pgp-expressing MDR cells. The Pgp blockers can restore the CsA retention in the MDR cells to its level in the Par cells.
多药耐药（MDR）肿瘤细胞上表达的P-糖蛋白（Pgp）分子可外排多种细胞抑制剂。在正常上皮和肿瘤上皮中，Pgp分子均选择性地表达于上皮细胞的顶端表面。这种分布似乎负责Pgp底物（包括环孢素A（CsA））从基底侧向顶端侧的跨细胞转运。一些正常淋巴细胞也表达少量Pgp分子，其功能尚不清楚。然而，Pgp阻滞剂可增强其有丝分裂原诱导的增殖对包括阿霉素和CsA在内的细胞抑制剂的敏感性。利用同位素标记的CsA和肿瘤淋巴细胞系，我们现在发现，与表达Pgp的MDR细胞相比，缺乏Pgp的亲本（“Par”）细胞中CsA的保留率更高。Pgp阻滞剂可将MDR细胞中CsA的保留率恢复到Par细胞中的水平。
