Prostaglandin and Its Receptors: Potential Targets for Gastrointestinal Inflammation and Cancer

Abstract

Prostaglandins are critical mediators of inflammation and promotes tumor cell proliferation, angiogenesis and metastasis. Cyclooxygenase (COX) is an important component in the biosynthesis of prostaglandins, which convert arachidonic acid to prostaglandin E2. Constitutively expressed COX-1 was found in many tissues and protects the gastrointestinal tract. On the other hand, COX-2 was induced during inflammation and cancer progression. Preclinical and clinical studies have demonstrated that non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors are promising therapeutic agents for gastrointestinal (GI) cancer prevention and treatment. Prolong use of COX-2 inhibitors cause renal and GI toxicities and increase cardiovascular risks which limit the use as an anti-cancer drug. PGE2 medicated its effect through binding to its receptors (EP1-EP4) that trigger different cellular signaling to incite tumor progression. This review recapitulates the important findings and signaling pathways of these EP receptors in inflammation and GI cancers. In particular, antagonism of EP2 and EP4 receptors have been extensively studied in vivo and in vitro with encouraging results, which may serve as potential effective therapeutic agents in treating against GI cancers