Loss of Mcl-1 expression sensitizes EGFR mutant cells to single-agent MEK inhibition. (A) EGFR mutant HCC827 cells were transfected with scrambled (sc) or Mcl-1 siRNA followed by treatment with either DMSO (-) or the indicated drugs for 30 h. Protein lysates were assessed with the indicated antibodies. (B) Cells were transfected and drug treated as in (A). Forty-eight hours following drug treatment, cells were assessed for subG0/G1 DNA content. (C) HCC827 cells were treated for 16 h with either DMSO (-) or the PI3K/mTOR dual inhibitor BEZ235 (.2 μM), the PI3K inhibitor, ZSTK474 (1 μM), or the AKT inhibitor, AKT 1/2 (1 μM), and cell lysates were prepared and subjected to immunoblotting with the indicated antibodies. (D) HCC827 cells were treated for 72 h with either DMSO (-) or indicated drugs, and cells were assessed for subG0/G1 DNA content. Mean + S.D. of triplicate experiments is shown. BEZ/AZD versus AKT/AZD, P < 0.001; BEZ/AZD versus ZST/AZD, P > 0.01, not significant.