Compared with HL-60, a higher percentage of HL-60/LR cells are in S phase of the cell cycle, have shorter doubling time, and are resistant to LAQ824-mediated growth inhibition. (A) Untreated and LAQ824-treated HL-60 versus HL-60/LR cells (at the indicated concentrations of LAQ824 for 24 hours) were counted, and the percentage of growth inhibition of the treated cells was calculated and depicted as the curves in the panel. Values on the curves represent the mean of 2 experiments performed in duplicate. (B) Equal numbers of the log-phase HL-60 versus HL-60/LR cells were started in culture, and aliquots of cells were withdrawn at the indicated intervals and counted. The values on the curves represent the mean numbers (of 2 experiments performed in duplicate) of cells at the indicated time interval. Error bars indicate SD. (Inset) The table in the panel shows the percentage of cells in the various phases of cell cycle, as determined by PI staining and DNA content analysis by flow cytometry. The values represent the means plus or minus SE of 3 experiments. (C) Groups of 6 NOD/SCID mice were injected with HL-60 or HL-60/LR cells and monitored. Survival of the mice was plotted, and median survival time was calculated. (D) HL-60 and HL-60/LR cells were stained with isotype controls or specific antibodies for MDR1, MRP1, LRP/MVP, and BCRP1 and then analyzed by flow cytometry. HL-60/VCR cells that express MDR1, LRP/MVP, and BCRP1 were used as a positive control. Open black-lined histograms represent the isotype control; filled gray histograms, specific antibody staining.