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

Abstract

Prostaglandin E2 plays important roles in carcinogenesis and malignant potential of prostate cancer (PC) by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of EP receptor antagonist are not clear. In this study, feed with or without EP1 receptor antagonist were given to a mouse model of prostate cancer. The mice were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using cleaved caspase-3. 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 survival period in the experimental group was significantly longer than that in the control group, and 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. Thus, an EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that EP1 receptor may be a novel chemopreventive agent for the development of PC.