Uveal melanoma cells develop resistance to BET inhibitors. A, Proliferation assays of uveal melanoma cell lines 92.1, Omm1.3, UM004, OMM1 (blue), and their resistant counterpart R-92.1, R-Omm1.3, R-UM004, R-OMM1 (red). Cell viability after 72 hours was calculated as percentage of untreated controls. Each point is a mean ± SD. B, The IC50s were calculated using the CompuSync software. The parental cell lines showed IC50 = 200–600 nmol/L, while for the resistant cells IC50 = 1,600–2,500 nmol/L. C, Parental and BETi-resistant cells were treated with DMSO or 0.5 μmmol/L PLX51107 for 48 hours, then stained with propidium iodide and analyzed for cell-cycle distribution by flow cytometry. The sub-G1 population was 23% for 92.1 and 17% for Omm1.3, while R-92.1 and R-Omm1.3 cells showed 4% and 3%, respectively. D, 92.1 and Omm1.3 cells were treated with 0.5 μmmol/L PLX51107 for up to 72 hours, and cell lysates were analyzed by immunoblotting for expression of c-Myc, PARP, and tubulin.