E-7869 (R-flurbiprofen) inhibits progression of prostate cancer in the TRAMP mouse

E-7869 (R-flurbiprofen) is a single enantiomer of a racemic nonsteroidal an ti-inflammatory drug. E-7869 does not inhibit either cyclooxygenase-1 or cy clooxygenase-2. We used the transgenic adenocarcinoma mouse prostate (TRAMP ) mouse, a prostate cancer model, to evaluate the effect of this drug on pr ostate cancer progression. Sixty 12-week-old male TRAMP mice were placed ra ndomly into five groups. The animals were treated by daily oral gavage with vehicle (1% carboxymethylcellulose) or E-7869 for 18-weeks. During the cou rse of the study, two diets were used. Three groups (vehicle, 15-mg/kg, and 20-mg/kg drug treatments) received a Teklad diet containing 2.4% saturated fat [a high saturated fat (HSF) diet], and two groups (vehicle and 20 mg/k g drug treatment) received an AIN-93G diet containing 1.05% saturated fat [ a low saturated fat (LSF) diet]. At necropsy, the urogenital system and per iaortic lymph nodes were removed and weighed. The prostate lobes, seminal v esicles, lungs, and periaortic lymph nodes were preserved and sectioned for histological evaluation. The lung and periaortic lymph nodes were graded a s to the presence (+) or absence (-) of metastasis; the urogenital tissues were graded on a 1-6 scale for degree of neoplasia/carcinoma. For both diet s, the urogenital wet weights and lymph node wet weights in the 20-mg/kg tr eatment groups were significantly lower as compared to vehicle control grou ps. In addition, treatment with 20 mg/kg E-7869 in the LSF diet group resul ted in a significantly lower primary tumor incidence (P < 0.05) and reduced incidence of metastasis. In this treatment group, the reduced incidence of metastasis was not statistically significant because the LSF diet itself r esulted in a remarkably lower incidence of metastasis in the vehicle contro l group (10% LSF versus 40% HSF). Treatment with 20 mg/kg E-7869 on the HSF diet resulted in a significantly lower incidence of metastasis (P < 0.05) and a reduction in the primary tumor incidence. These results suggest that E-7869 is a promising chemopreventive and treatment for human prostate canc er.