Figure 4. Therapeutic treatment with the LMP7 inhibitor ONX 0914 suppresses already established tumors in Apc^Min/+ mice.

A. Scheme of induction of colon tumorigenesis in Apc^Min/+ mice as accelerated by oral administration of 2 % DSS for 7 consecutive days. B. Five-week old Apc^Min/+ mice were treated every other day with either vehicle or 10 mg/kg ONX 0914 s.c. starting from day 14 (n ≥ 5). The body weight of individual mice was recorded daily during the DSS cycle or every other day after recovering to original weight. Data are illustrated as percent weight loss of the initial bw at day 0 of the experiment. Data points represent means ± SEM. C. Survival curve showing the percentage of mice remaining alive until the end of the experiment on day 35. D. On day 35 colons were removed and opened longitudinally for macroscopic assessment of tumor formation. Pictures are representative macroscopic views of colons on day 35. E. Colon tumor numbers of vehicle (grey triangles) or ONX 0914 (black dots) treated Apc^Min/+ scored on day 35 as defined by lesions ≥ 2 mm are displayed. Data are means ± SEM. F. Individual spleen weights of vehicle (grey triangles) or ONX 0914 (black dots) treated Apc^Min/+ on day 35 of treatment. Graph represents data as means ± SEM. Spleens of naïve 6-week old Apc^Min/+ mice were used as a control (white squares). G. Representative images of individual spleen sizes of vehicle or ONX 0914 treated Apc^Min/+ on day 35. Data have been compiled from two independent experiments. ****p<0.00005.