Figure 2. Latent HCC Cells Are Hypometabolic.

(A) Western blots demonstrating suppression of the mTOR pathway, as supported by decreased Phospho-S6 levels despite sustained mTOR levels, and activation of the AMPK pathway in three human HCC (449, 387 and HG2) cell lines and one rat (HR2) HCC cell line exposed to ischemic (I) as compared standard conditions (S). (B) Metabolomic profiling of cells grown under ischemic vs. standard conditions demonstrates a reduction in intermediates of purine and pyrimidine biosynthesis in human (SNU387) and rat (HR2) HCC cell lines. (C) NMR extracts of HR2 cells incubated with 1-¹³C-acetate and surviving ischemic conditions demonstrated significant reductions in the synthesis of de novo lipids as compared to cells grown under standard conditions (p=.0013). Similarly, bicinchoninic acid assay protein measurements demonstrated significant reductions in protein synthesis for HR2 cells surviving severe ischemia as compared to cells grown under standard conditions (p=.0086).