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. Author manuscript; available in PMC: 2016 Mar 30.
Published in final edited form as: Sci Signal. 2015 Dec 15;8(407):ra129. doi: 10.1126/scisignal.aac7235

Fig. 5. Global network shifts govern the apoptotic response to the combinatorial application of MEK and Akt inhibitors.

Fig. 5

(A and B) Mice were pretreated with the MEK inhibitor PD325901 (PD) or the MEK inhibitor CH5126766 (CH) in the presence or absence of the PI3K inhibitor NVP-BEZ235 (BEZ), as indicated, before being treated with TNF-α for the indicated times. Intestinal epithelia from the mice were then analyzed by quantitative Western blotting or Bio-Plex to determine (A) the relative abundance of cleaved caspase-3 (CC3), normalized to that of tubulin, as an indicator of apoptosis, and (B) the relative abundances of the indicated phosphoproteins. Data in (A) are means ± SEM of three experiments per time point, whereas data in (B) are means ± SEM of three or four experiments per time point. (C) The computational D-PLSR model derived from the DMSO, CH5126766-treated, and PD325901-treated conditions (from Fig. 3B). X's and ellipses represent centroids and 95% confidence intervals (CIs) (34) for the CH and CH+BEZ treatment groups, respectively. (D) Mice were pretreated with the MEK inhibitor CH5126766 (CH) in the presence or absence of the PI3K inhibitor NVP-BEZ235 (BEZ) or the Akt inhibitor MK2206 (MK), as indicated, before being treated with TNF-α for the indicated times. Intestinal epithelia from the mice were then analyzed by quantitative Western blotting or Bio-Plex to determine the relative abundance of cleaved caspase-3 (CC3), normalized to that of tubulin. Data are means ± SEM of two to five experiments per time point.