[Reversal of multidrug resistance of tumor cells by FG020327 and its mechanism].

BACKGROUND & OBJECTIVE: Over-expression of P-glyco-protein (P-gp) in tumor cells results in multidrug resistance (MDR), and failure of chemotherapy. Combined therapy of MDR-related cytotoxins plus MDR modulators is a promising strategy to overcome clinical MDR. This study was to explore MDR reversal activity of a novel compound FG020327, and its mechanism.

METHODS: MTT assay was used to evaluate MDR reversal activity of FG020327 in 2 P-gp expressing tumor cell lines, KBv200 and MCF-7/ADR. Adriamycin (ADM) accumulation in MCF-7/ADR cells was detected by fluorescence spectrophotometry. The effect of FG020327 on P-gp function was showed by rhodamine 123 (Rh123) accumulation and efflux in KBv200 cells.

RESULTS: FG020327 significantly enhanced sensitivity of MDR cells to anti- tumor drugs. Five mumol/L of FG020327 enhanced sensitivity of KBv200 cells to vincristine (VCR) by 44.9 folds, the reversal activity of which was 3 times that of verapamil (VRP). However, FG020327 had little effect on drug-sensitive MCF-7 cells and KB cells. FG020327 of 2.5, 5, and 10 mumol/L also enhanced ADM accumulation in MCF-7/ADR cells by 2.3, 2.7, and 3.7 folds, respectively, but didn't affect ADM accumulation in MCF-7 cells. FG020327 enhanced Rh123 accumulation in KBv200 cells,but not in KB cells.

CONCLUSIONS: FG020327 is an efficient modulator. The reversal of drug-resistance by FG020327 is probably related to enhanced anti-tumor drug accumulation, and inhibition of P-gp function in MDR tumor cells.