Figure 4. ATO and itraconazole combine to inhibit Hh pathway activation and tumor growth by SMOWT.
(A & B) Effect of combination therapy on the IC50 concentrations of itraconazole (A) or ATO (B) in NIH-3T3 cells expressing endogenous SMOWT stimulated with SHHN in 8×-GLI-luciferase signaling assays. Data represent mean of triplicates ± SD. (C & D) Nude mice with SMOWT hind-flank MB allografts were treated with vehicle control (40% cyclodextrin PO bid, N=7 tumors; black), GDC-0449 (100 mg/kg PO bid, N=7; red) ATO (7.5 mg/kg IP qd, N=7 tumors; green), itraconazole (75 mg/kg PO bid, N=7 tumors; blue), or both ATO and itraconazole (N=7 tumors; blue-green). Effect of GDC-0449, ATO, itraconazole, or the combination of ATO and itraconazole on (C) tumor growth and (D) Gli1 mRNA expression compared to vehicle control. Data represent group means ± SEM. *p < 0.01 vs. Vehicle; ** p < 0.01 vs. ATO alone; *** p < 0.01 vs. itraconazole alone. See also Figure S3, Table S2 and S3.
