Figure 7. Murine Medulloblastoma Cells Express Elevated Levels of CK1δ, the Inhibition of which Reduces Tumor Growth in vivo.

(A) CK1δ protein is overexpressed in Ptch1^+/−, Cdkn2^−/−, Trp53^−/−, and c-Myc tumors, whereas Wee1 is downregulated. Skp1 was used as a loading control. (B) Quantification of (A). (C-D) SR-1277 decreases proliferation of Ptch1^+/− allograft tumors. Ptch1^+/− tumor cells were injected subcutaneously into mice. Once the tumor reached a volume of 50 to 90 mm³, treatment with vehicle or SR-1277 (20 mg/kg, twice daily) was initiated. Tumor size was quantified in four samples for each time point, and the averages are shown. (D) An image showing representative SR-1277– treated (left) and vehicle-treated (right) tumors. (E) Proliferation of Cdkn2^−/−, Trp53^−/−, and c-Myc tumor cells is reduced in the presence of SR-1277. (F) Quantification of EdU incorporation into Cdkn2^−/−, Trp53^−/−, or c-Myc tumor cells after DMSO or SR-1277 treatment. (G) EdU-incorporation assay shows that proliferation of DAOY cells is reduced in the presence of SR-1277 (500 nM). (H-I) SR-1277 also reduces the intracranial growth of DAOY cells. (H) Twelve days after mice were transplanted with DAOY tumor cells, D-luciferin was administered intraperitoneally, and bioluminescence was measured. (I) Fluorescence imaging of representative mice in which DAOY cells were implanted intracraniallly and then treated with SR-1277 (20 mg/kg, twice daily) or vehicle for 21 days. Bioluminescence was quantified from the encircled regions that enclose the entire tumor. Results shown are the means ± SEM of three independent experiments (*p <0.05, **p <0.001, ***p <0.001).