Modesto Rita, Estarreja João, Silva Inês, Rocha João, Pinto Rui, Mateus Vanessa
H&TRC-Health and Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde de Lisboa, Instituto Politécnico de Lisboa, 1990-096 Lisbon, Portugal.
iMed.ULisboa, Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
J Clin Med. 2022 May 12;11(10):2739. doi: 10.3390/jcm11102739.
Animal models for colitis-associated colorectal cancer (CACC) represent an important tool to explore the mechanistic basis of cancer-related inflammation, providing important evidence that several inflammatory mediators play specific roles in the initiation and perpetuation of colitis and CACC. Although several original articles have been published describing the CACC model in rodents, there is no consensus about the induction method. This review aims to identify, summarize, compare, and discuss the chemical methods for the induction of CACC through the PRISMA methodology.
We searched MEDLINE via the Pubmed platform for studies published through March 2021, using a highly sensitive search expression. The inclusion criteria were only original articles, articles where a chemically-induced animal model of CACC is described, preclinical studies in vivo with rodents, and articles published in English.
Chemically inducible models typically begin with the administration of a carcinogenic compound (as azoxymethane (AOM) or 1,2-dimethylhydrazine (DMH)), and inflammation is caused by repeated cycles of colitis-inducing agents (such as 2,4,6-trinitrobenzenesulfonic acid (TNBS) or dextran sulfate sodium (DSS)). The strains mostly used are C57BL/6 and Balb/c with 5-6 weeks. To characterize the preclinical model, the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, angiogenesis markers such as proliferating cell nuclear antigen (PCNA), marker of proliferation Ki-67, and caspase 3, the presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of inflammation.
The AOM administration seems to be important to the CACC induction method, since the carcinogenic effect is achieved with just one administration. DSS has been the more used inflammatory agent; however, the TNBS contribution should be more studied, since it allows a reliable, robust, and a highly reproducible animal model of intestinal inflammation.
结肠炎相关结直肠癌（CACC）的动物模型是探索癌症相关炎症机制基础的重要工具，提供了重要证据表明几种炎症介质在结肠炎和CACC的发生及持续发展中发挥特定作用。尽管已经发表了几篇描述啮齿动物CACC模型的原始文章，但关于诱导方法尚无共识。本综述旨在通过PRISMA方法识别、总结、比较和讨论诱导CACC的化学方法。
我们通过Pubmed平台在MEDLINE中检索截至2021年3月发表的研究，使用高度敏感的检索表达式。纳入标准仅为原始文章、描述化学诱导的CACC动物模型的文章、啮齿动物体内的临床前研究以及以英文发表的文章。
化学诱导模型通常首先给予致癌化合物（如偶氮甲烷（AOM）或1,2 - 二甲基肼（DMH）），然后通过重复给予诱导结肠炎的药物（如2,4,6 - 三硝基苯磺酸（TNBS）或硫酸葡聚糖钠（DSS））引发炎症。最常用的品系是5 - 6周龄的C57BL/6和Balb/c。为了表征临床前模型，更多使用的参数包括体重、粪便稠度和发病率、炎症生物标志物如肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6和IL-1β、血管生成标志物如增殖细胞核抗原（PCNA）、增殖标志物Ki-67和半胱天冬酶3、溃疡的存在、结肠的厚度或充血情况以及炎症的组织学评估。
AOM给药似乎对CACC诱导方法很重要，因为仅一次给药就能产生致癌作用。DSS一直是使用较多的炎症诱导剂；然而，TNBS的作用应进一步研究，因为它能建立可靠、稳定且高度可重复的肠道炎症动物模型。
