Figure 10.

HI-511, a dual-target inhibitor against both AURKB and BRAF V600E, inhibited melanoma development in BRAFV 600E/PTEN-null mice. Melanoma was initiated in BRAF V600E/PTEN-null mice (6-8 weeks old) by local administration of 2.5 µL of 5 mM 4-HT by local application to the dorsal skin. At 23 days later, when the animals had readily measurable melanoma lesions, mice were randomly divided into 3 groups that were administered HI-511 (10 mg/kg B.W. n = 8), HI-511 (50 mg/kg B.W. n = 8) or vehicle control (n = 8). (A) Representative images of vehicle control or HI-511-treated mice after 36 days drug administration. (B) Tumor size in each of the treatment groups was measured every week. Tumor weight was measured at day 36. (C) Mice were euthanized, and melanoma specimens were disrupted and the expression of p-histone H3, histone 3, p-ERKs, ERKs, p-AKT, AKT, and GAPDH was assessed by Western blot. (D) Melanoma specimens were prepared for IHC staining for PCNA and Bcl-2; scale bars = 100 µm. Statistical significance was determined by one-way ANOVA and the asterisks indicate a significant decrease compared with vehicle control mice (*, p < 0.05; **, p < 0.01; ***, p < 0.001). Vemu: vemurafenib.