Karpisheh Vahid, Joshi Navneet, Zekiy Angelina Olegovna, Beyzai Behzad, Hojjat-Farsangi Mohammad, Namdar Afshin, Edalati Mahdi, Jadidi-Niaragh Farhad
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Biosciences, Mody University of Science and Technology, Lakshmangarh, Rajasthan, India.
Pathol Res Pract. 2020 Dec;216(12):153247. doi: 10.1016/j.prp.2020.153247. Epub 2020 Oct 19.
The most prevalent malignancy that can occur in the gastrointestinal tract is colon cancer. The current treatment options for colon cancer patients include chemotherapy, surgery, radiotherapy, immunotherapy, and targeted therapy. Although the chance of curing the disease in the early stages is high, there is no cure for almost all patients with advanced and metastatic disease. It has been found that over-activation of cyclooxygenase 2 (COX-2), followed by the production of prostaglandin E2 (PGE2) in patients with colon cancer are significantly increased. The tumorigenic function of COX-2 is mainly due to its role in the production of PGE2. PGE2, as a main generated prostanoid, has an essential role in growth and survival of colon cancer cell's. PGE2 exerts various effects in colon cancer cells including enhanced expansion, angiogenesis, survival, invasion, and migration. The signaling of PGE2 via the EP4 receptor has been shown to induce colon tumorigenesis. Moreover, the expression levels of the EP4 receptor significantly affect tumor growth and development. Overexpression of EP4 by various mechanisms increases survival and tumor vasculature in colon cancer cells. It seems that the pathway starting with COX2, continuing with PGE2, and ending with EP4 can promote the spread and growth of colon cancer. Therefore, targeting the COX-2/PGE2/EP4 axis can be considered as a worthy therapeutic approach to treat colon cancer. In this review, we have examined the role and different mechanisms that the EP4 receptor is involved in the development of colon cancer.
胃肠道中最常见的恶性肿瘤是结肠癌。目前结肠癌患者的治疗选择包括化疗、手术、放疗、免疫疗法和靶向疗法。尽管早期治愈该疾病的几率很高，但几乎所有晚期和转移性疾病患者都无法治愈。已发现结肠癌患者中环氧合酶2（COX-2）过度激活，随后前列腺素E2（PGE2）的产生显著增加。COX-2的致瘤功能主要归因于其在PGE2产生中的作用。PGE2作为主要产生的类前列腺素，在结肠癌细胞的生长和存活中起重要作用。PGE2在结肠癌细胞中发挥多种作用，包括增强增殖、血管生成、存活、侵袭和迁移。已证明PGE2通过EP4受体发出的信号可诱导结肠肿瘤发生。此外，EP4受体的表达水平显著影响肿瘤的生长和发展。通过各种机制使EP4过表达可增加结肠癌细胞的存活率和肿瘤血管生成。似乎从COX2开始、以PGE2延续并以EP4结束的途径可促进结肠癌的扩散和生长。因此，靶向COX-2/PGE2/EP4轴可被视为治疗结肠癌的一种有价值的治疗方法。在本综述中，我们研究了EP4受体在结肠癌发生发展中所涉及的作用和不同机制。
