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A chemical inflammatory agent that can induce colon cancer model

2020-12-07
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Dextran Sodium Sulfate (DSS) is a synthetic sulfate polysaccharide that can be used as an inflammatory agent to induce colon cancer models in mice. Oral administration of sodium dextran sulfate can directly damage colonic epithelial cells and induce inflammatory reactions by destroying the partition of commensal bacteria in the intestine. Colon cancer is a relatively common malignant tumor worldwide. Studies have found that about 5% of colon cancers are closely related to inflammatory bowel (IBD) diseases, and this type of colon cancer is also called inflammation-related Colon cancer. Although no model can fully simulate all the clinical manifestations and mechanisms of human inflammatory bowel disease, various mouse experimental colitis models or mouse colon cancer models have been established to study the pathogenesis of human IBD and colon cancer.

The dextran sodium sulfate model has been widely used to study the immune mechanism of colitis. Among them, activated caspase-1 plays a key role in the inflammation induced by dextran sodium sulfate, because the pathological performance of caspases-1 or NLRP3-deficient mice is significantly lower than that of wild-type (wT) mice, which is in line with IL-1B and IL The decrease of -18 level is related, indicating that excessive production of IL-18 can aggravate dextran sodium sulfate-induced colitis.

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The intestinal mucosal barrier plays an important role in the occurrence and development of ulcerative colitis (UC). When the intestinal mucosal barrier is destroyed, the permeability of the intestine increases, which easily leads to the occurrence of intestinal inflammation. Some researchers compared the differences in the mouse chronic UC model induced by different concentrations of dextran sodium sulfate (DSS), and selected the optimal DSS concentration to induce UC in mice, and then used the optimal DSS concentration to build the chronic ulcerative colon of the mouse. Inflammation model, using Western blot, Real-time PCR and other experimental methods to explore the role of IL-22 in DSS-induced chronic ulcerative colitis and its close relationship with the intestinal mucosa Connecting the relationship between occludin protein and STAT3 protein provides a new therapeutic target and theoretical basis for the treatment of UC [1]. The study found that the mouse chronic UC model can be successfully replicated when DSS solution is administered periodically. The 2.5% DSS group has a lower mortality rate and better model stability; IL-22 can effectively alleviate the chronic ulcer induced by DSS in mice The inflammatory response of colitis may be caused by regulating the STAT3 pathway to increase the expression of tight junction protein occludin in the intestinal mucosal barrier.

Acute inflammation induced by sodium dextran sulfate and exposure to the microbiota can lead to changes in DNA methylation and open chromatin of regulatory elements, which leads to changes in the expression of functional genes related to colitis and colon cancer. In biological research, azomethane oxide (AOM) and dextran sodium sulfate are often used to construct inflammation-related mouse colon cancer models.

The development of inflammatory tissues to dysplasia and eventually cancer is an important link in the development of colon cancer. Building a colon cancer model that can simulate the occurrence and development of human diseases is a powerful tool for studying colon cancer. After years of accumulation of pharmacological service experience, Medicilon has established a complete tumor animal model library, and can provide various effective tumor animal models according to customer needs to test the effectiveness of drugs. According to the characteristics of various tumor models, immunodeficient mice are selected as experimental animals.

Among various colon cancer models, inflammation-related colon cancer models induced by AOM/DSS are more common. For example, researchers have explored the effects of different drug doses, dosing cycles and exposure times in the use of azoxymethane (AOM) and AOM combined with dextran sodium sulfate (DSS) on the effect of establishing colon cancer induction models in C57BL/6J mice [2]. The researchers were given low, medium, and high concentrations of AOM (10, 15, 20 mg/kg, once a week for 4 weeks, 24 in each group, 24 in the AOM control group) or AOM (10 mg/kg) combined DSS (first, second, and third cycles, the number of mice were 50, 41, 29, and 40 in the DSS control group) intervention, and the gross and histopathological evaluation of the colorectum of mice killed at different time points after administration.

Results AOM alone can produce abnormal crypt foci (ACF) in the colon of mice. With the increase of AOM drug concentration and/or exposure time, the number of ACF increased significantly (P<0.05). AOM combined with DSS can form adenomas with high-grade intraepithelial neoplasia in the mouse colon. Compared with the first cycle of DSS, the second and third cycles of DSS can significantly increase the incidence of tumors, the average number of tumors, and the average number of tumors in tumor-bearing mice. And tumor volume. The study found that colorectal ACF of C57BL/6J mice increased with the increase of AOM concentration and exposure days. AOM combined with DSS can accelerate the occurrence of colorectal cancer models, and increasing DSS circulation can increase tumor formation efficiency.

At present, DSS model animals have been widely recognized and can be used to study the etiology and pathogenesis of ulcerative colitis; immunological research in inflammatory response; treatment of ulcerative colitis, research and development of anti-inflammatory drugs, and the mechanism of inflammation-related cancer formation Research, and the mouse colon cancer model induced by AOM/DSS can well simulate the physiopathological process of chronic intestinal inflammation-induced cancer.

[1] The effect of IL-22 on occludin in the intestinal mucosa of mice with chronic ulcerative colitis induced by DSS [J].

[2] A comparative study of establishing C57BL/6J mouse colon cancer induction model by AOM and AOM combined with DSS [J].

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