Growth-Factor-Driven Rescue to Receptor Tyrosine Kinase (RTK) Inhibitors through Akt and Erk Phosphorylation in Pediatric Low Grade Astrocytoma and Ependymoma
Fig 3
Growth-factor-driven rescue to RTK inhibitors.
A, Human growth factor antibody array showing overall low growth factor release by pediatric low grade astrocytoma and ependymoma cell lines (mean ± SD), except for FGF. B, Cell counting assays showing mean effect (± SD) of growth factors on the different tumor cell lines in the absence of inhibitors (*p < 0.05). C, Heat map showing the effect of growth factors on tumor cells treated with different TKI’s. Growth-factor-driven rescue during RTK inhibition was calculated with the formula: ((A = LC50 of cells treated with inhibitor plus growth factor)–(B = LC50 of the inhibitor-treated cells only)) / B x 100% if (A—SD)–(B + SD) > 0, otherwise it was defined as ‘no rescue’ (purple squares). If addition of the growth factor did affect the LC50 during RTK inhibition, this was marked as ‘partial rescue’ (yellow/orange squares). Complete rescue was noted as A > 10x B (red squares). As an internal negative control no growth-factor-driven rescue was found of the particular RTK ligand of which the receptor is inhibited. D, Cell viability assays demonstrating various effects of growth factors on TKI-treated cells (mean ± SD), with a corresponding colored bar indicating the level of growth-factor-driven rescue.