Urbanska Aleksandra Malgorzata, Zhang Xiaoying, Prakash Satya
Biomedical Technology and Cell Therapy Research Laboratory, Departments of Biomedical Engineering, Physiology, and Artificial Cells and Organs Research Center, McGill University, 3775 University Street, Montreal, QC, H3A 2B4, Canada.
National Hepatobiliary and Enteric Surgery Research Center, Ministry of Health, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
Cell Biochem Biophys. 2015 Jul;72(3):757-69. doi: 10.1007/s12013-015-0528-5.
Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions between the intestinal microbiota, colonic epithelial barrier, and host immune system, are also discussed.
肠道炎症是全球范围内增加结直肠癌（CRC）发病率的主要因素之一。胃肠道炎症与疾病早期的肿瘤发展直接相关，因此是预防和治疗结肠肿瘤的关键问题。因此，使用抗炎药物首先作为一种策略，用于减少许多炎症性肠病（IBD）中的慢性炎症，但已通过降低结肠肿瘤形成的风险证明了其有效性。这篇综述强调了慢性炎症，主要是在IBD中，在CRC发生发展中的作用，包括具有致瘤作用的分子和免疫机制。多条证据表明，几种用作抗炎药物的生物活性和植物化学化合物也具有抗肿瘤特性。本文还讨论了口服细胞因子和小分子的用途，以及作为抗炎治疗的关键膳食补充剂。此外，强调了关于CRC和肠道炎症的全面知识，以及肠黏膜壁作为黏膜免疫屏障在与肠道微生物群（病原体和共生菌）、腔内分泌物（胆汁酸、细菌和上皮代谢物）以及摄入化学物质（食物成分、高脂肪含量、杂环胺和膳食纤维摄入量低）相互作用时所起的重要作用。几种抗炎药物的多功能性为它们不仅在IBD而且在CRC的治疗和预防中的应用开辟了道路。目前用于口服递送抗炎剂的生物工程方法，包括细胞因子、基因工程细菌或炎症小分子抑制剂，直接有助于CRC的早期管理。本文还讨论了当前治疗方法的局限性，这些局限性源于对肠道微生物群、结肠上皮屏障和宿主免疫系统之间复杂分子相互作用的不完全理解。
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