Figure 6

Cdc42 blockade by AZA197 suppresses tumor growth and prolongs animal survival. A Left panel: representative images of human SW620 tumor xenografts on day 22 from mice treated with solvent (Control) or 100 μg/day AZA197 (AZA197 d22) (bar = 10 mm). Right panel: AZA197 significantly suppresses tumor weight of human colon cancer xenografts in mice. Data are shown as mean tumor weights on day 22. *, significantly different from control on day 22 (P = 0.006). B Effect of AZA197 on proliferation in SW620 xenografts. Left panel: representative immunohistochemistry images of tumor tissue sections from mice treated with solvent (Control) or 100 μg/day AZA197 on day 22 stained with Ki-67 antibody (bar = 200 μm). Right panel: Quantitative histomorphometric analysis of Ki-67-positive, proliferating tumor cells. *, significantly different from control (P = 0.046). C Effect of AZA197 on apoptosis in SW620 xenografts. TUNEL labeling of cells undergoing DNA fragmentation: Left panel: representative images of tumor tissue sections from mice treated with solvent (Control) or 100 μg/day AZA197 on day 22 (bar = 50 μm). Right panel: Quantitative histomorphometric analysis of TUNEL-positive, apoptotic tumor cells. *, significantly different from control (P = 0.035). D Analysis of total Cdc42 protein expression and levels of PAK1 and ERK phosphorylation in SW620 colon cancer tissue on day 22 from mice treated with solvent (Control) or 100 μg/day AZA197 (AZA197 d22). Representative Western blot images and quantification of immunoblots stained with Cdc42, PAK1 and phospho-PAK1/2 (pPAK), ERK and phospho-ERK antibodies. Cdc42 blockade by AZA197 reduces PAK1/2 and ERK phosphorylation in SW620 tumor tissue. *, significantly different from control. E Effect of AZA197 treatment on animal survival in SW620 colon cancer bearing mice. Kaplan-Meier survival curves for controls and AZA197 treated mice. AZA197 significantly prolongs animal survival.*, significantly different to control (P = 0.042).