Levels of proapoptotic BH3-only Bim protein and antiapoptotic Mcl-1 protein play a critical role in drug combination-induced apoptosis. A, OCI/AMl3 cells were electroporated with Bim siRNA or scrambled siRNA for 24 hours, treated with AZD8055 (0.4 μmol/L) and/or selumetinib (0.2 μmol/L) for 48 hours, and examined for apoptosis induction. Inset: knockdown of basal level of Bim protein expression. B, OCI/AML3 cells were transferred with Mcl-1 shRNA or shGFP control lentiviral vectors, the puromycin-selected cells were treated with AZD8055 (0.4 μmol/L) and/or selumetinib (0.4 μmol/L) for 48 hours, and examined for apoptosis induction. Inset: knockdown of basal level of Mcl-1 after puromycin selection. DMSO, dimethyl sulfoxide, control. ** P < 0.01.