| Objective (s):①To observe the effect of deoxycholic acid inducing the carcinogenesis of colorectal tumor in APCmin/+ mice. ②To investigate the effect of on the expression of COX-2 in colorectal tumor tissue of mice induced by deoxycho-lic acid.Methods:①30 only four weeks of APCmin/+ mice were randomly divided into control group (sterilized water),0.2% DCA experimental group (sterilized water containing 0.2%DCA), use of natural water intake, the mice were killed after 5 weeks of intervented, compare the number, size, volume and distribution of colorectal tumors in the mice of each group. ②Detection and comparison of COX-2 expression in colorectal tumor tissue of each group of mice by Western-Blot.Results: ①Mice in the experimental group began to decrease in body weight at third weeks of feeding DCA, compared with the control group, the body weight was reduced in fifth weeks(P<0.01). The body weight of the control group was increased at fifth weeks compared with the beginning of the experiment(P<0.001). During the experiment, Two groups of mice showed no difference in the average time of hematochezia and prolapse(p=0.637,p=0.537). ②In terms of the number of colorectal tumors in mice, the number of intestinal tumor in experimental group was significantly higher than that in control group(P=0.039). In the experimental group and control group, colorectal tumors mainly occurred at the distal end of the rectum. The incidence of colorectal cancer in the experimental group was significantly increased compared with the control group(P=0.038). According to different size of the tumor size, In the experimental group, colorectal tumors were mainly happened in diameter of 2-4mm (medium) tumors, while the control group of colorectal tumors mainly happened in diameter less than 2mm (small) tumors; The number of colorectal tumors in the experimental group was significantly increased compared with the control group in diameter 4-6mm (larger) and 2-4mm(medium) tumors (P=0.002,P<0.001), but it wasn’t like that in diameter less than 2mm (small) and greater than 6mm(larger) tumors (P=0.456,P=0.695). ③In terms of tumor size, the size of colorectal tumor in the experimental group was significantly larger than that in the control group (P=0.004).④In terms of tumor volume, the total volume of colorectal tumor in the experimental group was significantly higher than that in the control group(P=0.005). According to the different parts of the tumor stratification, experimental group of colorectal tumor volume compared with the control group, there were statistically significant differences (P=0.004), But there was no significant difference between the experimental group and the control group in the middle of the colorectal cancer (P=0.057, P=0.634);According to the size of the tumor size, the two groups had no significant difference in diameter less than 2mm; compared with the control group, the tumor volume of two groups of 2-4mm and 4-6mm were significantly higher than that of the control group, the control group dad no tumor in diameter>6mm happened. ⑤The HE pathological results of mice colorectal tumors results showed:in the experimental group, there were 8 cases of adenocarcinoma,1 cases of high grade intraepithelial neoplasia and 1 cases of polyp; in the control group, there were 3 cases of adenocarcinoma,1 cases of high grade intraepithelial neoplasia, 5 cases of polyp,3 cases of non tumor lesions. The incidence of colorectal cancer in the experimental group and the control group were 80% and 25% respectively (P=0.08),the tumor incidence was 90% and 75% respectively (P=0.045). Western-blot purpose of the strip and the gray value of the relative quantitative analysis of the results show that the expression of COX-2 in colorectal tumor tissue of experimental group was significantly higher than that in control group (P=0.021).Conclusion(s): ①The deoxycholic acid promotes the development of colorectal cancer in APCmin/+mice. ②The deoxycholic acid can promote the expression of COX-2 in colorectal tumor tissue of APCmin/+ mice, it prompt that DCA can promote the development of colorectal cancer in APCmin/+ mice, its because of activating or promoting the expression and activity of inflammatory factors in the related pathway, so as to play its role in promoting the carcinogenesis of intestinal adenoma in APCmin/+ mice. Due to the specific inhibitors of the COX-2 associated pathway, the further research is helpful to reveal the mechanism of the occurrence and development of CRC and its mechanism from a new perspective, To provide a new target for the prevention and treatment of CRC. |
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