Department of Gynecology and Obstetrics, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665, Kongjiang Road, Yangpu District, Shanghai, 200000, People's Republic of China.
Department of Obstetrics and Gynecology, Ludwig-Maximilians University of Munich, Campus Großhadern: Marchioninistraße 15, 81377, Munich, Germany.
Arch Gynecol Obstet. 2020 Jun;301(6):1365-1375. doi: 10.1007/s00404-020-05559-6. Epub 2020 May 3.
Nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (COXibs) inhibit the progression of endometrial cancer, ovarian cancer and cervical cancer. However, concerning the adverse effects of NSAIDs and COXibs, it is still urgent and necessary to explore novel and specific anti-inflammation targets for potential chemoprevention. The signaling of cyclooxygenase 2-prostaglandin E-prostaglandin E receptors (COX-2-PGE-EPs) is the central inflammatory pathway involved in the gynecological carcinogenesis.
Literature searches were performed to the function of COX-2-PGE-EPs in gynecological malignancies.
This review provides an overview of the current knowledge of COX-2-PGE-EPs signaling in endometrial cancer, ovarian cancer and cervical cancer. Many studies demonstrated the upregulated expression of the whole signaling pathway in gynecological malignancies and some focused on the function of COX-2 and cAMP-linked EP2/EP4 and EP3 signaling pathway in gynecological cancer. By contrast, roles of EP1 and the exact pathological mechanisms have not been completely clarified. The studies concerning EP receptors in gynecological cancers highlight the potential advantage of combining COX enzyme inhibitors with EP receptor antagonists as therapeutic agents in gynecological cancers.
EPs represent promising anti-inflammation biomarkers for gynecological cancer and may be novel treatment targets in the near future.
非甾体抗炎药(NSAIDs)和选择性环氧化酶-2 抑制剂(COXibs)可抑制子宫内膜癌、卵巢癌和宫颈癌的进展。然而,鉴于 NSAIDs 和 COXibs 的不良反应,探索新型、特异的抗炎靶点用于潜在的化学预防仍然是紧迫且必要的。环氧化酶-2-前列腺素 E-前列腺素 E 受体(COX-2-PGE-EP)信号通路是参与妇科肿瘤发生的中心炎症通路。
对 COX-2-PGE-EP 在妇科恶性肿瘤中的作用进行了文献检索。
本综述概述了 COX-2-PGE-EP 信号通路在子宫内膜癌、卵巢癌和宫颈癌中的最新知识。许多研究表明,整个信号通路在妇科恶性肿瘤中呈上调表达,一些研究则集中于 COX-2 以及 cAMP 相关的 EP2/EP4 和 EP3 信号通路在妇科癌症中的功能。相比之下,EP1 的作用及其确切的病理机制尚未完全阐明。关于 EP 受体在妇科癌症中的研究强调了将 COX 酶抑制剂与 EP 受体拮抗剂联合作为妇科癌症治疗药物的潜在优势。
EP 是妇科癌症有前景的抗炎生物标志物,可能成为未来的新型治疗靶点。