Figure 4
From: Inhibition of Bcl-2/Bcl-xL and c-MET causes synthetic lethality in model systems of glioblastoma
c-MET inhibition reprograms glioblastoma energy metabolism by suppression of oxidative phosphorylation. (A) LN229 GBM cells were treated with DMSO, ABT263, Crizotinib (Crizo) or the combination of both and analyzed by extracellular flux analysis on a Seahorse XF24 device (Agilent, Inc.) in the context of a mitochondrial stress test. This assay records the base line oxygen consumption rate of cells (Basal OCR), followed by the injection of Oligomycin (O), the uncoupler (FCCP) and Antimycin/Rotenone (A/R). In addition, we recorded extracellular acidification rate (ECAR) simultaneously along with OCR. Shown are mean values with SD. (B) Calculation of individual OXPHOS related parameters are displayed. Shown are mean values with SD. (C) LN229 and U87 GBM cells were treated with ABT263, Crizotinib or the combination as indicated. Thereafter, ATP levels were assessed in comparison to the control treated cells. Shown are means and SD. ABT: ABT263, Crizo: Crizotinib. (D) LN229 and U87 GBM cells were treated with ABT263, Crizotinib or the combination for 1d. Thereafter, whole cell protein lysates were prepared and analyzed for the expression of p-AMPK (threonine 172) or AMPK by capillary electrophoresis. Concentrations are in μM.
