Fig. 4.

Effects of the SK inhibitor ABC294640 (50 mg/kg dose) on cell survival pathways in CD45− cells (non-inflammatory cells, assuming mostly colon epithelial cells) and CD45+ (mostly inflammatory cells). Beclin-1 is a putative tumor suppressor, which plays a key role in autophagy. AKT phosphorylation and ERK1/2 phosphorylation are associated with cell survival. The finding that ABC294640 can increase Beclin-1 and suppress the phosphorylation of AKT and ERK1/2, especially in epithelial cells, gives us insight into the unpinning mechanisms associated with the suppression of colitis-driven colon cancer by ABC294640.