Figure 3. Inhibition of MEK abrogates VS-5584-induced phosphorylation of ERK, but substantially enhances VS-5584-induced cell death in a cell line-selective fashion.
(A and B) BxPC-3 and HPAC cells were treated with vehicle control, 2 μM VS-5584 (VS), 1 μM GSK1120212 (GSK), or 2 μM VS plus 1 μM GSK (Combo) for 48 h. Whole cell lysates were subjected to Western blotting and probed with the indicated antibody. The fold changes for the densitometry measurements, normalized to β-actin and then compared to no drug treatment control, are indicated. (C and D) BxPC-3 and HPAC cells were treated with vehicle control or the indicated drugs for 48 h. Cells were fixed with 80% ice-cold ethanol and stained with PI for cell cycle analysis. The percentage of cells with sub-G1 DNA content are graphed as means of triplicates ± SEM from one representative experiment. ***indicates p < 0.001; combined treatment compared to individual treatments and control. (E and F) BxPC-3 and HPAC cells were treated with vehicle control or the indicated drugs for 48 h. Whole cell lysates were subjected to Western blotting and probed with anti-PARP or -β-actin antibody.