A novel bioassay for P-glycoprotein functionality using cytochalasin D

摘要: The functional contribution of both P-glycoprotein (P-gp) and the multidrug resistance-associated protein (MRP) to resistance (MDR) in tumor cells is commonly determined by drug cytotoxicity and/or accumulation/efflux tests. We report on a bioassay developed for specific detection P-gp levels efficacy related chemosensitizers (CD-P-gp-assay). assay based flow cytometric measurement changes HG2M cell cycle compartment which are due induction polykaryons after exposure proliferating three defined cytochalasin D (CD) concentrations with without verapamil. As demonstrated 13 well-characterized MDR models (20 resistant sublines), there significant correlation between cytokinesis-blocking CD doses, as well responsiveness MDR1 gene expression (mRNA P-gp) allowing discrimination different P-gpMDR. CD-P-gp-assay specificity was assessed testing 23 compounds: 19 known potent inhibitors P-gp-MDR, some them, though lesser extent, also MRP-MDR; 1 inhibiting MRP-but not P-gpMDR; 3 inactive types MDR. A modulation activity confined exclusively P-gp-expressing lines chemosensitizers. cytoskeletal measured FACS sensitive tool detect Cytometry 31:187‐198, 1998. r 1998 Wiley-Liss, Inc.