Abstract #2091: Chemopreventive efficacy of meloxicam against prostate tumor growth and progression in the prostate-specific PTEN conditional gene knockout mouse model

High incidence of prostate cancer in older men suggests that agents that inhibit or delay the disease process could be beneficial in reducing cancer mortality and morbidity. Increased expression of COX-2 has been found in most of the cancers and compelling evidence from genetic and clinical studies indicates that COX-2 upregulation is one of the key steps in carcinogenesis. There is a strong body of evidence pointing out the role of cox-2 early in the prostate carcinogenesis model, particularly in the progression of prostatic intraepithelial neoplasia lesions to prostate carcinoma. Epidemiological data suggests that treatments with non-steroidal anti-inflammatory drugs (NSAIDs) were associated with reduced risk in a number of malignancies. We evaluated the chemopreventive efficacy of meloxicam, a selective COX-2 inhibitor, against prostate cancer in prostate-specific PTEN conditional gene knockout mice. Mice were fed meloxicam (1 mg/kg/day) in drinking water during 10 to 16 weeks of age. Our data demonstrated no bodyweight differences between treated and untreated controls. Pathological findingsshowed that meloxicam-fed mice had a 37% lower incidence of prostate cancer compared to mice in the control group. Immunohistochemical analysis revealed that meloxicam treatment did in fact reduce COX-2 expression without inhibiting COX-1. Meloxicam-fed showed reduced proliferation rates as well as increases in apoptotic rates as measured by PCNA immunohistochemistry and TUNEL assay, respectively. Moreover, there was a decrease of reactive stroma seen as well a reduction of VEGF expression in tumors and tumor stroma. These results suggest that meloxicam safely inhibits tumor growth and progression in the PTEN knockout mouse model by antiproliferative, proapoptotic and antiangiogenic effects thus suggesting its chemopreventive potential against human prostate cancer.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2091.