Establishing the colitis-associated cancer progression mouse models.
Inflammatory bowel disease (IBD) has been reported as an important inducer of colorectal cancer (CRC). The most malignant IBD-associated CRC type has been highlighted as colitis-associated cancer (CAC). However, lack of CAC cases and difficulties of the long follow-up research have challenged researchers in molecular mechanism probing. Here, we established pre-CAC mouse models (dextran sulfate sodium [DSS] group and azoxymethane [AOM] group) and CAC mouse model (DSS/AOM group) to mimic human CAC development through singly or combinational treatment with DSS and AOM followed by disease activity index analysis. We found that these CAC mice showed much more severe disease phenotype, including serious diarrhea, body weight loss, rectal prolapse and bleeding, bloody stool, tumor burden, and bad survival. By detecting expression patterns of several therapeutic targets-Apc, p53, Kras, and TNF-α-in these mouse models through western blot, histology analysis, qRT-PCR, and ELISA methods, we found that the oncogene Kras expression remained unchanged, while the tumor suppressors-Apc and p53 expression were both significantly downregulated with malignancy progression from pre-CAC to CAC, and TNF-α level was elevated the most in CAC mice blood which is of potential clinical use. These data indicated the successful establishment of CAC development mouse models, which mimics human CAC well both in disease phenotype and molecular level, and highlighted the promoting role of inflammation in CAC progression. This useful tool will facilitate the further study in CAC molecular mechanism.
Department of Gastroenterology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China.
Haiming
H
Zheng
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Zhanjun
Z
Lu
Department of Gastroenterology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China.
Ruhua
R
Wang
Department of Gastroenterology, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai, China niweichen2015@126.com.
Niwei
N
Chen
Department of Gastroenterology, Shanghai East Hospital, Tongji University, Shanghai, China.
Ping
P
Zheng
D000818:Animals; D003092:Colitis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D017491:Genes, APC; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
Apc; Kras; TNF-α; azoxymethane (AOM); colitis-associated cancer mouse model; dextran sulfate sodium (DSS); inflammation; p53
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