Supplementary Figure 2 from The Phosphoinositide 3-Kinase α Selective Inhibitor BYL719 Enhances the Effect of the Protein Kinase C Inhibitor AEB071 in GNAQ/GNA11-Mutant Uveal Melanoma Cells

PDF file - 405KB, AEB071/ BYL719 combination inhibits in vivo tumor growth in a GNA11 mutant xenograft model. A, Suppression of PKC/ ERK and PI3Kalpha/AKT pathways in Omm1 GNA11. Cells were treated with indicated AEB071/BYL719 concentrations for 2, 6 and 24 hrs and Western blots were then performed. alpha-Tubulin was used as a loading control. MARCKS and S6 inhibition was present but no AKT inhibition occurred with combination. ERK was inhibited by BYL719. B, AEB071/BYL719 inhibited tumor growth in a Omm1 xenograft model. AEB071/BYL719 inhibited tumor growth in a xenograft model with the GNA11 mutant Omm1 cell line. 6-8 week athymic female mice were subcutaneously injected with Omm1 cells. Drug treatments began after tumors reached 100 mm3. Mice with tumors were treated three times daily with AEB071 (80mg/kg/d) or once daily with BYL719 (50 mg/kg/d) or in combination for 5 days each week for a total of 3 weeks. Tumors were measured with calipers every 2 to 3 days. Tumor volume was compared between groups of mice at various points in time AEB071 or BYL719 alone. Toxicity was measured by weight loss.