STAT3信号在炎症性肠病及结肠炎相关结直肠癌发生发展中的作用和相关药物研究进展  

The role of STAT3 in inflammatory bowel disease and colitis-associated cancer and research progress of the related drugs

作　　者：程晓范 朱胡太龙 刘灵 罗靖 孙志洁 董德利 CHENG Xiao-fan;ZHU Hu-tai-long;LIU Ling;LUO Jing;SUN Zhi-jie;DONG De-li(School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China)

机构地区：[1]中国药科大学药学院,江苏南京211198

出　　处：《药学学报》2022年第8期2253-2261,共9页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金面上资助项目(82170472).

摘　　要：信号转导和转录激活因子3(signal transducer and activator of transcription 3,STAT3)是维持细胞增殖和存活的重要因子,可被多种细胞因子激活进而介导免疫和炎症反应以应对损伤。炎症性肠病(inflammatory bowel disease,IBD)是一种慢性肠道炎症性疾病,主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD)两种形式。在IBD肠组织中STAT3被多种促炎细胞因子异常激活,破坏肠道屏障完整性、过度激活肠道中固有免疫和Th17细胞介导的免疫应答,导致IBD肠道长期处于炎症状态,最终引起肠道纤维化、肠腔狭窄等并发症。除对免疫反应的调节外,STAT3也通过促进纤维化相关基因转录参与IBD肠道纤维化。结肠炎相关结肠癌(colitis-associated cancer,CAC)是结直肠癌中特别具有侵袭性的亚型,与长期慢性炎症引起的IBD相关。STAT3与CAC的发生发展也密切相关,STAT3在肿瘤中过度激活,抑制肿瘤中免疫细胞的肿瘤杀伤活性,并促进癌细胞增殖、血管生成及肿瘤的侵袭和迁移。本文综述STAT3信号在炎症性肠病及结肠炎相关结直肠癌发生发展中的作用及以STAT3信号为靶点的药物研发最新进展。Signal transducer and activator of transcription(STAT)3 is a critical transcription factor for cell proliferation and survival.It is activated within cells by many cytokines to mediate immune and inflammatory responses to injury.Inflammatory bowel disease(IBD),represented by Crohn′s disease(CD)and ulcerative colitis(UC),is a chronic inflammatory disease of the intestinal tract.STAT3 has been shown to be abnormally activated in IBD colon tissues by many pro-inflammatory cytokines,leading to disruption of the intestinal mucosal barrier and excessive innate immune and Th17 responses.The persistent chronic inflammation eventually leads to intestinal fibrosis and stenosis.In addition to immune responses,STAT3 is also involved in intestinal fibrosis in IBD by promoting the transcription of fibrosis-related genes.Colitis-associated cancer(CAC)is a particularly aggressive subtype of colorectal cancer and is associated with chronic inflammation-induced IBD.STAT3 has also been associated with CAC initiation and development.STAT3 is overactivated in tumors,which leads to suppression of the anti-tumor activity of immune cells and promotion of cancer cell proliferation,tumor angiogenesis,invasion,and migration.In the present article,we summarize the role of STAT3 in IBD and CAC and the research progress of the related drugs developed for UC and CAC treatment.

关 键 词：信号转导和转录激活因子3 溃疡性结肠炎 克罗恩病 炎症性肠病 结肠癌 肠道屏障 免疫 炎症 

分 类 号：R966[医药卫生—药理学]