Frejborg Ellen, Salo Tuula, Salem Abdelhakim
Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, 00014 Helsinki, Finland.
Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, 00014 Helsinki, Finland.
Int J Mol Sci. 2020 Dec 3;21(23):9246. doi: 10.3390/ijms21239246.
The cyclooxygenase-2 (COX-2) is a potent enzyme that converts arachidonic acid to prostaglandins (PG), including PGE2, a key mediator of inflammation and angiogenesis. Importantly, COX-2 is activated in response to inflammatory stimuli, where it is also believed to promote the development and progression of head and neck cancers (HNC). COX-2 can mediate its protumorigenic effect through various mechanisms, such as inducing cell proliferation, inhibition of apoptosis, and suppressing the host's immune response. Furthermore, COX-2 can induce the production of vascular endothelial growth factors, hence, promoting angiogenesis. Indeed, the ability of COX-2 inhibitors to selectively restrict the proliferation of tumor cells and mediating apoptosis provides promising therapeutic targets for cancer patients. Thus, in this comprehensive review, we summarized the reported differential expression patterns of COX-2 in different stages of head and neck carcinogenesis-from potentially premalignant lesions to invasive carcinomas. Furthermore, we examined the available meta-analysis evidence for COX-2 role in the carcinogenesis of HNC. Finally, further understanding of the biological processes of COX-2 and its role in orchestrating cell proliferation, apoptosis, and angiogenesis may give therapeutically beneficial insight to develop the management plan of HNC patients and improve their clinical outcomes.
环氧化酶-2(COX-2)是一种强效酶,可将花生四烯酸转化为前列腺素(PG),包括PGE2,后者是炎症和血管生成的关键介质。重要的是,COX-2在炎症刺激下被激活,人们还认为它会促进头颈癌(HNC)的发生和发展。COX-2可通过多种机制介导其促肿瘤作用,如诱导细胞增殖、抑制细胞凋亡以及抑制宿主免疫反应。此外,COX-2可诱导血管内皮生长因子的产生,从而促进血管生成。事实上,COX-2抑制剂选择性限制肿瘤细胞增殖并介导细胞凋亡的能力为癌症患者提供了有前景的治疗靶点。因此,在这篇综述中,我们总结了已报道的COX-2在头颈癌发生不同阶段——从潜在的癌前病变到浸润性癌——中的差异表达模式。此外,我们研究了关于COX-2在头颈癌发生中作用的现有荟萃分析证据。最后,进一步了解COX-2的生物学过程及其在协调细胞增殖、凋亡和血管生成中的作用,可能为制定头颈癌患者的管理计划并改善其临床结局提供有益的治疗见解。