Figure 6. SGI-1776 displays anti-tumor activity in combination with a BRAF inhibitor in vivo.

(A) NSG mice were xenotransplanted with 1205Lu melanoma cells and tumors were allowed to grow above 200 mm³. Mice were then treated with the single agents SGI-1776 (100 mg/kg 3×/week), or PLX4720 (200 mg/kg diet), or with the combination of both drugs. Tumor volumes were measured at the indicated time points. Statistical analyses of tumor volumes used one-way ANOVA with groups defined by treatment (p < 0.001 for all comparisons shown). Error bars represent SEM, n = 10 mice. (B) PIM kinase expression (all three isoforms) in mouse tumor lysates (n = 2/group); Histone H3 serves as a loading control. Lysates were collected 3 days after treatment initiation. (C) Western blot analyses of mouse tumor lysates (n = 3/group) isolated on day 17 of the experiment shown in (A). Effectors of the PI3K, MAPK, and STAT3 signaling pathways, as well as pBAD and the tumor suppressor p27, were evaluated. Histone H3 served as loading control.