Oral administration of E-type prostanoid (EP) 1 receptor antagonist suppresses carcinogenesis and development of prostate cancer via upregulation of apoptosis in an animal model.

Prostaglandin E2 plays an important role in carcinogenesis and malignant potential of prostate cancer (PC) cells by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of the EP receptor antagonist are unclear. In this study, we used a mouse model of PC. The mice were provided standard feed (control) or feed containing the EP1 receptor antagonist and were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using a cleaved caspase-3 assay. The incidence of cancer in the experimental group was significantly lower than that in the control group at 15, 30, and 52 weeks of age. The percentage of poorly differentiated PC cells was significantly lower in the experimental group than in the control group at 30 and 52 weeks of age. The percentage of apoptotic cells in the experimental group was significantly higher than that in the control group at 15, 30, and 52 weeks of age. These findings indicate that feeding with the addition of EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that the EP1 receptor antagonist may be a novel chemopreventive agent for PC.