Inhibition of COX-2 suppresses renal tumorigenesis and inhibits the progression of xenograft tumor of TSC2-deficient cells in preclinical models. (a and b) Tsc2^+/− mice were treated with either vehicle or Celecoxib (0.1% in mouse chow) for one month, and then sacrificed for analysis at the end of treatment. Renal cystadenoma histology and microscopic kidney tumor scores were assessed. (a) Microscopic kidney tumor scores are plotted on a linear scale (P = 0.0002). Data are analyzed from 16 vehicle and 11 Celecoxib treatment groups. (b) Two cystadenomas are shown. Results are representatives of 11 or 16 mice per group. Bar, 100 µM. (c–g) Female CB17-scid mice were inoculated with ELT3-luciferase cells subcutaneously. Mice were treated with either vehicle or aspirin (100 mg/kg/day in the drinking water) for 3 wk (n = 9). Results are representative of five to eight mice per group. (c and d) Bioluminescent imaging was performed weekly. Bioluminescent intensity in xenograft tumors was recorded and quantified weekly. Data are the mean of bioluminescent intensity in tumors from five to eight mice per group. (e) Tumor area was normalized to the baseline before drug administration. Data represent the mean of tumor area from five to eight mice per group. (f) Immunoblot analysis of COX-2, c-Myc, and phospho-S6 in xenograft tumors from mice treated with aspirin or vehicle. Results represent tumors from five mice from each group. (g) Mouse urinary levels of PGE₂ were measured (ELISA). Data represent the mean of PGE₂ levels from five to eight mice per group. *, P < 0.05; **, P < 0.01; ***, P < 0.001; two-way ANOVA test.