Effect of STI571 and ATRA alone or in combination on the differentiation and growth of ATRA-sensitive and ATRA-resistant myeloid cell lines.
The ATRA-sensitive NB4, HL-60, and U937 cells as well as the ATRA-resistant NB4-derived sublines NB4.306, NB4.007, and NB4.R1 cells were seeded at an initial concentration of 2 × 105/mL and treated for 4 days with vehicle alone (control, ■), STI571 (▨, 5 × 10−6 M; 1 × 10−5 M in the case of HL-60), ATRA (░, 10−7 M), or the combination of the 2 compounds (▪). (A) The level of NBT-reducing activity was measured in the indicated cell line. (B) The level of NBT-reducing activity (left panel); the percentage of CD11b, CD11c, or CD33 (middle panel); and the total number of viable cells (right panel) were determined in NB4.R1 cells (the percentage of cell viability is shown above columns). Results are the mean ± SD of 3 separate culture dishes and are representative of at least 2 independent experiments. *, significantly lower than the corresponding group treated with medium alone (P < .01 according to the Student t test). °°, significantly higher than the sum of the effects observed in the corresponding STI571- and ATRA-treated groups, following 2-way analysis of variance and measurement of the F of interaction (P < .01 according to Tukey test).
