Article Figures & Data
Figures
- FIGURE 1.
MET mechanism of action. MET activates AMPK (main energy sensor in cells), mimicking starvation conditions inside cells. In response to AMPK activation, all energy-consuming pathways are downregulated and adenosine triphosphate–producing mechanisms (such as glycolysis) are increased. CoA = coenzyme A; mTOR = mammalian target of rapamycin; TSC = tuberous sclerosis complex.
- FIGURE 2.
MET-mediated activation of AMPK. (A) Results of Western blotting for expression of AMPK, phosphorylated AMPK (pAMPK), and β-actin internal control in HT29 and MC26 cells after 24 h of MET treatment. (B) Semiquantitative analysis after gating of AMPK expression–to–actin expression ratio to 100% shows severalfold increases in phosphorylation and dose-dependent activation of AMPK in both cell lines.
- FIGURE 3.
Alteration of 18F-FDG uptake after MET treatment. MET treatment caused increased 18F-FDG retention in both HT29 and MC26 cell lines. Results were corrected for decay and cell count and are presented as mean ± SEM (n = 10) percentage of initial activity absorbed/106 cells.
- FIGURE 4.
Effect of MET on 18F-FLT retention. MET treatment decreased 18F-FLT retention in both HT29 and MC26 cell lines. Results were corrected for decay and cell count and are presented as mean ± SEM (n = 10) percentage of initial activity absorbed/106 cells.
- FIGURE 5.
Effect of MET on proliferation. (A) Decreased relative percentages of cells in S phase of cell cycle (normalized to control at 100%) were observed in both cell lines (HT29 and MC26) after treatment with MET. Data are presented as mean ± SEM (n = 3). (B) Representative flow cytometry results from control and treatment groups of MC26 cells (10 mM MET for 24 h), with S-phase cells gated in P2 window.
- FIGURE 6.
Increases in tumor 18F-FDG uptake and decreases in 18F-FLT uptake after MET therapy. PET images were acquired before (0 h) and after (24 h) MET therapy (500 mg/kg) in HT29 tumor–bearing animals. (A and B) Representative 18F-FDG (A) and18F-FLT (B) PET scans before and after treatment. (C) SUVs before and after treatment (mean ± SEM; n = 3; imaged with both tracers). *Statistically significant difference (P < 0.05). White arrows indicate HT29 tumors.
