title: Cyclooxygenase-1 and -2: molecular targets for cervical neoplasia.
abstract: Cyclooxygenase (COX) is a key enzyme responsible for inflammation, converting arachidonic acid to prostaglandin and thromboxane. COX has at least two isoforms, COX-1 and COX-2. While COX-1 is constitutively expressed in most tissues for maintaining physiologic homeostasis, COX-2 is induced by inflammatory stimuli including cytokines and growth factors. Many studies have shown that COX-2 contributes to cancer development and progression in various types of malignancy including cervical cancer. Human papillomavirus, a necessary cause of cervical cancer, induces COX-2 expression via E5, E6 and E7 oncoproteins, which leads to prostaglandin E2 increase and the loss of E-cadherin, promotes cell proliferation and production of vascular endothelial growth factor. It is strongly suggested that COX-2 is associated with cancer development and progression such as lymph node metastasis. Many studies have suggested that non-selective COX-2 inhibitors such as non-steroidal anti-inflammatory drugs (NSAIDs), and selective COX-2 inhibitors might show anti-cancer activity in COX-2 -dependent and -independent manners. Two phase II trials for patients with locally advanced cervical cancer showed that celecoxib increased toxicities associated with radiotherapy. Contrary to these discouraging results, two phase II clinical trials, using rofecoxib and celecoxib, demonstrated the promising chemopreventive effect for patients with cervical intraepithelial neoplasia 2 or 3. However, these agents cause a rare, but serious, cardiovascular complication in spite of gastrointestinal protection in comparison with NSAIDs. Recent pharmacogenomic studies have showed that the new strategy for overcoming the limitation in clinical application of COX-2 inhibitors shed light on the use of them as a chemopreventive method.
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul.
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul.
authors.forename: Taehun
authors.initials: T
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul.
authors.forename: Mi-Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam.
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Suh
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul.
authors.forename: Hyun Hoon
authors.initials: HH
authors.lastname: Chung
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul ; Cancer Research Institute, Seoul National University College of Medicine ; Major in Biomodulation, World Class University, Seoul National University, Seoul, Korea.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Song
keywords: Cervical cancer; Cyclooxygenase; Cyclooxygenase-2 inhibitor