Effect of MEK inhibition on activity of of APO2L/TRAIL and chemotherapy in HD cell lines. MEK inhibition potentiated the effect of APO2L/TRAIL and chemotherapy in HD cell lines. (A) The HD-LM2 cell line was incubated with DMSO, UO126 (25 μM), APO2L/TRAIL (1 μg/mL), or the combination of UO126 plus TRAIL for 72 hours. Viable cell numbers were determined by the MTS assay. Results are mean of 3 independent experiments performed in triplicate (± SEM). (B) A representative experiment showing the effect of UO126 and TRAIL on the HD-LM2 cells. Tumor cells were incubated as described in the legend to panel A for 48 hours. Cell-cycle analysis and cell death were determined by the PI staining method. Percentages of dead cells are shown for each condition. The added activity of the combination of APO2L/TRAIL and UO126 was due to increased cell death. (C) Effect of UO126 (25 μM) on doxorubicin chemotherapy (0.1 μg/mL)–induced cell death in the L-428 and HD-MYZ cell lines. Results are presented as the mean of 3 independent experiments performed in triplicate (± SEM). Cell viability was determined by MTS assay after 48 hours of incubation.