Figure 3. Treatment with the LMP7 inhibitor ONX 0914 suppresses intestinal tumorigenesis in Apc^Min/+ mice.

A. Scheme of experimental procedures: Induction of colon tumorigenesis was accelerated by oral administration of 2 % DSS for 7 consecutive days. Five-week old Apc^Min/+ or Apc^Min/+LMP7^-/- mice were treated every other day with either vehicle or 10 mg/kg ONX 0914 s.c. from day 0 of the DSS cycle until the endpoint of the Apc^Min/DSS protocol on day 35 (n ≥ 5). B. Body weight of vehicle (grey triangles) or inhibitor (black dots) treated Apc^Min/+ mice and Apc^Min/+LMP7^-/- mice (blue squares) was recorded daily during the DSS cycle and every other day after recovering to original weight. Data are illustrated as percent weight loss (y-axis) plotted versus time (x-axis). Data points represent means ± SEM. C. Survival curve showing the percentage of vehicle or ONX 0914 treated Apc^Min/+ mice and Apc^Min/+LMP7^-/- mice remaining alive until the end of the experiment on day 35. D. On day 20 or 35 after beginning of the experiment, colons were removed and opened longitudinally for semi quantitative macroscopic analysis of colonic tumor formation. Pictures are representative macroscopic views of colons on day 35. E. Graph shows tumor number per mouse as defined by lesions ≥ 2 mm. Data are means ± SEM. F. Average colon length on day 35 of vehicle (grey column) or ONX 0914 (black column) treated Apc^Min/+ and untreated Apc^Min/+/LMP7^-/- mice (blue column). G. H&E stainings of colon sections of vehicle or ONX 0914 treated Apc^Min/+ mice on day 35 were quantified according to the grading of the respective tumor types that are low-grade dysplasia (light grey), high-grade dysplasia (grey) or adenocarcinoma (black). The percentage of mice having no tumors are represented by white bars. H. Individual spleen weight on treatment day 35 of vehicle or ONX 0914 treated Apc^Min/+ and Apc^Min/+LMP7^-/- mice. Graph represents data as means ± SEM. Data are compiled from two independent experiments. ***p < 0.0005, ****p < 0.00005.