Progress in Prevention and Treatment of Dysplasia in Ulcerative Colitis Based on Cyclooxygenase-2/p53 Axis

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Dec;46(6):940-948. doi: 10.3881/j.issn.1000-503X.15911.

Abstract

Ulcerative colitis(UC)is a chronic inflammatory bowel disease characterized by non-specific,persistent inflammation in the intestines.This chronic inflammation often increases the risk of serious complications such as colorectal cancer.Dysplasia acts as a driver of cancer development and plays a connecting role in the occurrence and development of chronic intestinal inflammation and colorectal cancer.Cell proliferation/apoptosis imbalance is the driving factor for dysplasia development.The abnormal proliferation/apoptosis of intestinal mucosal epithelial cells may be affected by cyclooxygenase-2(COX-2),tumor suppressor gene p53,or both.Therefore,reasonable regulation of COX-2/p53 axis may be a key to achieving intestinal mucosal proliferation/apoptosis balance.This article discusses the effects and mechanism of COX-2 and p53 in regulating the occurrence and development of dysplasia in UC from the proliferation/apoptosis imbalance of intestinal mucosal epithelial cells,aiming to provide a reference for understanding the mechanism of dysplasia in UC and developing targeted therapeutic drugs.

溃疡性结肠炎(UC)是一种慢性炎症性肠病,非特异性、持续的肠道炎症为其主要特征,这种慢性炎症往往会增加罹患结直肠癌等严重并发症的风险。异型增生作为推动癌症发展的后备军,对慢性肠道炎症与结直肠癌的发生发展起到衔接作用。而细胞增殖/凋亡失衡则是异型增生发展的驱动因素。其中,肠黏膜上皮细胞增殖/凋亡异常可能受环氧合酶-2(COX-2)、抑癌基因p53及二者串扰关系的影响,对COX-2/p53轴的合理调控可能是实现肠黏膜增殖/凋亡平衡的关键。本文从肠黏膜上皮增殖/凋亡失衡入手,思考COX-2、p53在UC异型增生发生发展中的影响及其具体作用机制,以期为UC异型增生疾病机制及靶向治疗药物的开发提供参考。.

Keywords: cyclooxygenase-2; dysplasia; p53 gene; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Apoptosis
  • Cell Proliferation
  • Colitis, Ulcerative* / metabolism
  • Colitis, Ulcerative* / pathology
  • Cyclooxygenase 2* / metabolism
  • Humans
  • Intestinal Mucosa / metabolism
  • Tumor Suppressor Protein p53* / metabolism

Substances

  • Cyclooxygenase 2
  • Tumor Suppressor Protein p53