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. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: Cancer Res. 2015 Dec 16;76(3):675–685. doi: 10.1158/0008-5472.CAN-15-1141

Figure 3.

Figure 3

Disruption of the PI3K/AKT pathway affects EZH2 expression in NSCLC cell lines with mutant KRASG12D and KRASG12S, and the combination of AKTi with EZH2i results in a significant increased sensitivity in vitro and in vivo to PI3K/AKT targeted therapy in cells expressing mutant KRASG12D. A and B, EZH2, AKT, and phospho-AKT expression in NSCLC and HBEC cell lines. KRASWT and KRAS mutants were treated with different doses of the AKTi MK2206 (0, 25, and 50 nM). C, EZH2 and AKT expression in NSCLC cell lines upon knockdown of AKT expression by treatment with siAKT. D, Pharmacologic inhibition of EZH2 with DZNep in combination with AKT inhibition. (Data are graphed as the mean percent increase ± percent standard deviation). Treatment with DZNep decrease MK2206 IC50, 2.0-fold (P < 0.05) in cells expressing KRASG12D and a 2.2-fold (P < 0.05) in cells expressing KRASG12S. E, Athymic nude mice were inoculated with HCC461 cell lines expressing KRASG12D and then treated with vehicle, DZNep, MK2206, or a combination of DZNep plus MK2206. Tumor volume was determined for each treatment. (*P < 0.05; **P < 0.03, ***P < 0.001).