In vitro nuclear analysis of MDR mediated by Pgp and usage of MDR reversing agents

Abstract: Objective Aim at finding simple but effect methods to estimate the MDR of tumor cells and the effect of reversing agents to provide useful message to problems encountered in clinical chemotherapy. Method 2×106 cells of human myelogeneous leukemia cell line K562 and its resistant subline (K562/D)were incubated with 8MBq 99Tcm-MIBI, observed the 99Tcm-MIBI accumulation with presence of reversal agents cyclosporin A(0.1～0.4μg/ml) and/or verapamil(2.5～10μg/ml) at various time intervals. Results ①Different concentration of verapamil or cyclosporin A significantly increased the 99Tcm-MIBI uptake of K562 resistant subline, while the uptake of K562 cell line expressing nondetectable Pgp was not affected. ②combination of low dose verapamil (2.5μg/ml) and cycolsporin A (0.1μg/ml) had similar effect on 99Tcm-MIBI accumulation with higher dose of inhibitor lonely. Conclutions Increase of 99Tcm-MIBI uptake may indirectly reflect the effect of the MDR reversal agents. Combination of lower dosages of modulators may play same reverse effect with less side effects, this provide new useful message to clinical chemotherapy.