Figure 6.

The ERK and USP9x inhibitors inhibits the stimulative effect of obesity on metastases in vivo. A, Diet-induced obesity in ovariectomized (OVX) athymic nude mice that were fed with a high fat sucrose diet (HFSD). A standard chow-based diet (Chow) was used as the control diet (n=8/group). The mice were fed the diets for 12 weeks and the body weight of each mouse was measured every week. B, Tumor growth and metastasis in diet-induced obese OVX athymic nude mice versus the control animal group with the regular diet. After six weeks of feeding, luciferase-labeled 4TO7 tumor cells were implanted into the mammary fat pad on the right side of mice. One week after cell inoculations, PD0325901 was administered to mice (25 mg/kg dose) by gavage three times a week. Control mice were treated with vehicle by the same route. Tumor-bearing mice were administered with WP1130 suspension (40 mg/kg, i.p.) every other day. Six weeks after inoculation, mice were intraperitoneally injected with fluorescein substrate (1.5 mg/10 g). After anesthesia with saturated avertin (0.18 ml/10 g, i.p.), mice were placed in a Small Animal in Vivo Imaging System and images were acquired. C, The photon quantity in each mice group was analyzed (bottom), *p<0.05 vs Chow/Control; #p<0.05 vs HFSD/Control. D, Percentage of mice with lung metastases, as determined by lung bioluminescence.