Co-targeting AKT and PDK1 is effective in repressing MAPK4-induced cancer cell growth.

(A) Western blot on the engineered SUM159 and HCC1806 cells with 0.5 μg/ml Dox-induced overexpression of MAPK4 (iMAPK4) or control (iCtrl), treated with 2 μm or 5 μm of PDK1 inhibitor GSK2334470 or DMSO control. (B) Western blots and (C) proliferation assays on the engineered SUM159 and HCC1806 cells with 0.5 μg/ml Dox-induced overexpression of MAPK4 (iMAPK4) or control (iCtrl). The cells were also treated with DMSO control, PDK1 inhibitor GSK2334470 (2 μm), AKT inhibitor MK2206 (2 μm), or both inhibitors. (D) Western blots and (E) proliferation assays on the WT and MAPK4-KO MDA-MB-231 cells treated with DMSO control, PDK1 inhibitor GSK2334470 (1 μm), AKT inhibitor MK2206 (1 μm), or both inhibitors. Data are means ± SD from at least 3 separate experiments. P values by two-way ANOVA followed by Sidak’s multiple comparisons. ns, not significant, ****P S1 Data. MAPK4, mitogen-activated protein kinase 4; PDK1, phosphoinositide-dependent kinase-1; WT, wild type.