A, PI3kα siRNA inhibits AKT phosphorylation in uveal melanoma cell lines. siRNA knockdown of p110α isoform was performed with or without AEB071 in 92.1, Mel270, Omm1.3 (GNAQ mutant), and Mel290, C918 (WT) cell lines. A non-specific siRNA was used as control. Western blots of PI3Kα, AKT, MARCKS, ERK, S6 and cleaved PARP were then performed. The nuclear protein Ku70 was used as a loading control. B, PI3Kα and PKC inhibition reduces cell proliferation in GNAQ mutant uveal melanoma. Cell viability was assessed after transfection, with or without AEB071 for 5 days. C, Structure of BYL719. D, BYL719 inhibits AKT (ser473) phosphorylation, and/or p-ERK in some cell lines. Cells were treated with indicated concentrations of BYL719 for 24 hrs, and analyzed for pAKT, pERK, pS6 and the respective total proteins. α-Tubulin was used as a loading control. E, BYL719 as single agent has minimal to no effect on cell viability in uveal melanoma after 5 days of exposure. Concentrations tested include 0, 10, 100,1000 nM. Results represent the mean of three independent experiments.