Preliminary study on 5-aminosalicylic acid in a mouse model of colitis-associated carcinoma / 中华消化杂志

ABSTRACT

Objective To investigate the expressions of peroxisome proliferator activated receptor-γ (PPAR-γ) and β-catenin in 5-aminosalicylic acid （ASA) intervened colitis carcinogenesis mouse model induced by azoxymethane (AOM) and dextran sulfate sodium (DSS).Methods Thirtysix BALB/c mice were evenly divided into control group,model group,and intervention group.For model group and intervention group,mice were intraperitoneally injected with AOM (10 mg/kg) one day before experiment,then drank 4％ DSS solution freely for one week and followed with common drinking water for another two weeks.Taking 4％ DSS solution and common drinking water repeated for three cycles.For intervention group,5-ASA (150 mg/kg) was given from three days before experiment to the end of research.For control group,mice were intraperitoneally injected with 0.9％NaCl solation and then given common drinking water for nine weeks.The symptoms of the disease were monitored in mice and pathological changes of tissues were evaluated at the end of first week and ninth week.At the end of the ninth week,the expressions of PPAR-γ,β-catenin protein and PPAR-γat mRNA level in colon tissue were detected.The data were analyzed by t test.Results The colitis disease activity index (DAI) index of intervention group was 1.81 ±0.59 after drinking DSS solution for one week and the number of tumor was 4.11 ± 1.05 at the end of the ninth week,both were significantly lower than those of model group (2.47 ± 0.53 and 9.71±2.29 respectively,t=2.88 and 6.55; both P＜0.01).The expression of PPAR-γ at protein level (2.11±1.36) and mRNA level (1.45±0.10) in colon tissue of intervention group significantly increased compared with those of model group (0.43±0.53 and 0.57±0.08 respectively,t=3.07 and 18.99,both P＜0.01).There was no significant difference of β-catenin expression among groups (P＞0.05).Conclusions 5-ASA can efficiently improve the inflammatory reaction and tumor load in AOM and DSS induced colitis carcinogenesis mouse model,and at the same time can promote the expression of PPAR-γ in colon.However,there was no significant influence on the expression of β-catenin.