Fig 5. Effect of MLN8237 on GTML spheres and mice.

(A) PC projections of 96 cells from WT1, WT2, M10519 cells treated with and without dox, and M10519 cells with 100nM MLN8237. PC1 and PC2 captured 21% and 13% of variances in the dataset. (B) MYCN stability in MLN8237-treated M10519 cells. Cells were incubated with dox or MLN8237, and cell extracts were analyzed by western blotting. (C) Kaplan-Meier curves for overall survival of mice having orthotopic tumors treated with (red) or without MLN8237 (blue). 250 cells were transplanted in to the cerebellum of FBVN mice, and once the tumor burden reached at a level of 1x10⁹ photon/s, mice were daily treated twice with (n = 8) or without (n = 9) MLN8237 (daily oral dosing at 60mg/kg). Mice were treated with MLN8237 for 5 days and then untreated for 2 days, and then the repeat this schedule twice more.