Combined Targeting of BRAF and CRAF or BRAF and PI3K Effector Pathways Is Required for Efficacy in NRAS Mutant Tumors
Figure 2
Effect of BRAF and PIK3CA knock-down on KRASG13D mutant HCT116 cell growth.
(A) Western blot analysis of PIK3CA or BRAF knock-down in HCT116 at 72 h post dox induction of relevant shRNAs. The effect of knock-down on the phosphorylation status of relevant downstream targets is shown. (B) Proliferation of BRAF and PIK3CA shRNA expressing cells 4 days post dox treatment. (C) shRNA targeting PIK3CA when induced in mice bearing HCT116 tumors did not delay tumor growth. (D) BRAF knock-down in HCT116 derived tumors shows a trend towards delayed tumor growth. Each data point is the mean±SEM tumor volume derived from 10 mice. Dotted line in (C, D) represents data from dox treated animals.