Fig. 4: DHODH is a therapeutic target in neuroblastoma.

A Dose–response curves for BRQ and GSK983 in indicated human neuroblastoma cell lines following four days of treatment. Data are mean ± SD (n = 4). B IC50 values for BRQ and GSK983 in the indicated cell lines following four days of treatment. Data are mean ± SD from at least two independent experiments (four technical replicates for each cell line per experiment). C, D Cell-growth assays of indicated neuroblastoma cell lines treated with DMSO (vehicle control), BRQ, or GSK983 in the absence (Ctrl) or presence of supplemental orotate (C) or uridine (Urd, D) for two or four days. Data are mean ± SD (n = 4). P values were determined by two-tailed Student’s t-test. ***P < 0.001. E, F Tumor-growth (E) and event-free survival (F) curves for mice-bearing xenografts of BE(2)-C or SMS-KCNR cells treated with vehicle or BRQ at 50 mg/kg every three days. Log-rank test P values are indicated. G, H Tumor growth (G) and event-free survival (H) of mice bearing established xenografts of BE(2)-C cells treated with vehicle or BRQ at 25 mg/kg every other day. Log-rank test P value is indicated.