Figure 2. Pharmacological inhibition of p38 synergizes with AZD1208 through reduced mTOR signaling.
A.-E. p38 inhibitors enhance AZD1208 response. OCI-M1, OCI-M2, U2932, K562, and TMD8 cells were treated with increasing concentrations of AZD1208 (x-axis) and co-treated with the p38 inhibitor SB202190. Viability was measured after 5 days using CellTiter-Blue (n = 3). F. p38 inhibitors are synergistic with AZD1208. OCI-M1, OCI-M2, U2932, K562, and TMD8 cells were treated with 2-fold dilutions of AZD1208, SB202190, SCIO-469, or combinations for 5 days. Viability was assessed by CellTiter-Blue and used to calculate synergy scores. Self-self combination treatments were used as a baseline to determine significance (n = 3). P-values were calculated using a one-way ANOVA and Dunnett's test. p ≤ 0.05 (*), p ≤ 0.01 (**), p ≤ 0.001 (***), and p ≤ 0.0001 (****) G. Combined inhibition of PIM and p38 results in reduced AKT/mTOR signaling after 48 hours. OCI-M1 (2.105 cells/well in 6-well plate) and OCI-M2 (4.105 cells/well in 6-well plate) cells were treated for 48 hours with 2 μM AZD1208, 20 μM SB202190, or the combination. Cell lysates were harvested and subjected to western blot analysis (n = 3).
