ATRA/FK228 have combined effects on P-gp expression, and the P-gp inhibitor PSC833 reverses cytoprotective effects of ATRA/FK228. (A) Flow cytometric analysis of the P-gp expression using a PE-conjugated anti–P-gp antibody or a PE-conjugated isotype control antibody (IgG1). (i) NB4 control cells. (ii) NB4 cells treated with the ATRA (1.0 μM)/FK228 (3.0 nM) combination for 72 hours. (iii) HL60 DOX cells as the positive control. The data shown are representative of 2 experiments that produced comparable results. (B) Flow cytometric analysis of the Rh123 efflux in the presence/absence of PSC833. (i) Control NB4 cells and (ii) NB4 cells treated with the ATRA (1.0 μM)/FK228 (3.0 nM) combination for 72 hours. (iii) HL60 DOX cells as the positive control. The data are representative of 2 experiments that produced comparable results. Percentage of apoptotic annexin V–positive cells (Ci-ii) or cell viability detected by trypan blue–negative cell numbers (Di-ii) following 48- and 72-hour treatment with the ATRA (1.0 μM)/FK228 (3.0 nM) combination with or without PSC833 (1 μM) given 24 hours prior to DOX (17.0 nM). The mean ± SD of results were from 3 independent experiments and statistically significant differences were determined by ANOVA and Fisher post hoc tests (^*P < .05).