THE CIRCUMVENTION OF TUMOR MULTIDRUG RESISTANCE BY BULLATACIN AND ITS MECHANISM

AIM: To find new drugs to overcome tumor multidrug resitance(MDR), bullatacin was studied with technique of cell culture in vitro. METHODS: The study was carried out using two pairs of cell lines: MDR cell lines and their parental sensitive cell lines including MCF-7/Adr cells and MCF-7 cells, KBv200 cells and KB cells. Cytotoxicity was determined with tetrazolium (MTT) assay. The function of P-gp was examined by Fura-2/AM assay. Cellular accumulation of adriamycin(ADM) was determined by fluorescence spectrophotometry measurement (to reflect cellular bullatacin accumulation). RESULTS: Bullatacin showed potent cytotoxicity to MCF-7/Adr cells, MCF-7 cells, KBv200 cells and KB cells. The cytotoxicities of bullatacin to MDR cells were similar to that to parental sensitive cells. Bullatacin markedly increased cellular Fura-2 and ADM accumulation in MCF-7/Adr cells, while not in MCF-7 cells. CONCLUSION: There was no cross-resistance of bullatacin to P-glycoprotein-positive MCF-7/ADR and KBv200 cell lines as compared with their sensitive cell lines. The mechanism of overcoming MDR was associated with the decrease of P-gp function and the increase of MDR cellular drug accumulation.