| The relationship of stress and tumor is recently a hot topic. Glucocorticoids (GCs) is a kind of the most important stress hormones in the human body, which both have strong immunosuppressive effects, and affect the biological behavior of tumor cells by changing the microenvironment of tumor cells.what’s more,GCs can directly regulate the proliferation, apoptosis and invasion of tumor cells. GCs is widely used in clinical treatment, such as chronic diseases and solid tumors during chemotherapy, whicih also increase the level of GCs in the human body besides the stress. Therefore it is vital to know the effect of GCs on the occurrence and progression of tumor. The occurrence and progression of colorectal cancer is influenced by many factors, and inflammation is considered to be important one. In view of the complicated effects of GCs on colorectal cancer, there are studies which showed the relationship of GCs and tumor progression on the immunodeficient mices in vivo and tumor cells in vitro, but the results are not concordant. In a word, the effect of GCs on occurrence and progression of colorectal cancer is not very clear in vivo with the normal immune system.ObjectiveTo establish the colitis-associated colorectal carcinoma model which is induced spontaneously by azoxymethane/dextran sodium sulfate(AOM/DSS) in male mice of C57BL/6 type and evaluate the effects of eleveated levels of corticosterone on occurrence and development of colorectal cancer in mice through the tumor gross morphology and pathological examination.Method1. Establishment of the AOM/DSS mouse model. C57BL/6 male mice were were given an intraperitoneal injection with AOM (12.5 mg/kg) on the 1st day, followed by 2.5% DSS treatment in drinking water for 5 days after 7 days and by drinking water without DSS for 14 days. DSS/water treatment cycle was repeated another 2 times. The body weight change, stoool appearance and stool blood occult were recorded and calculate the disease activity index(DAI). The mice were sacrificed and dissected the colorectum on the 78th day. And then assessed tumor formation grossly and evaluated pathological results microscopically.2. Corticosterone (50mg/L) in drinking water was given to the model mice and corticosterone release agents (7.5mg-60 days) were implanted subcutaneously in the model mice 1 week after the end of the third round of DSS in drinking water. All the mice of the experimental group and the control group were taken blood from the ciliary venous plexus and killed 31 days after the interventions of the corticosterone. The concentration of the corticosterone in plasma was tested by the radioimmunoassay. And then the colorectum was dissected and the tumor was measured by electronic vernier caliper. The tumor tissure was examined by H&E staining and immunohistochemical staining (PCNA,p-STAT3, Bcl-xL,NF-κB (p65)and COX-2).Tumor gross morphology (including tumor multiplicity, tumor size distribution, tumor area and volume of per mouse) and pathological results (inflammation score and immunohistochemical score) were assessed between the experimental group and the control group.Result1. DAI of mice in model group was significantly higher than that of control group (2.93 vs.O). The mortality rate of the model mice was 10%. Colorectal tumor incidence of the model group was 88.9%, and the tumor was confirmed as colorectal adenocarcinoma by pathological examination. However, the mice of control group had no death and no tumor occurred.2. The corticosterone concentration in plasma of corticosterone in drinking water group and the control group was significantly different (123.7ng/ml vs.80.95ng/ml, P<0.05). There was no obvious difference in general condition of the two groups of mice. The tumor count(13.38 vs.7.88,P<0.01), tumor area(100.7mm2 vs.48.28 mm,P<0.01) and volume(133.6mm3vs.60.26 mm3, P<0.05) per mouse of the corticosterone in drinking water group was greater than the control group, which was significant different, but there was no difference in tumor size distribution (P>0.05).The inflammation score of cancer tissue in pathological examination of the corticosterone in drinking water group was significantly lower compared with the control group(P<0.01).The expression and immunohistochemistry score of NF-κB (p65), p-STAT3, COX-2, and Bcl-xL in corticosterone treated group was not significantly different with the control group(P>0.05).3. The corticosterone concentration in plasma of corticosterone of the corticosterone subcutaneously implanted group and the control group were not significantly different. General condition, gross morphology and pathology of the two groups were not significantly different (P>0.05).Conclusion1. The colorectal cancer model in mice which was induced by AOM/DSS is a stable and reliable model of spontaneous tumor and is suitable for in-depth study of colorectal cancer.2. The corticosterone water can significantly elevate the concentration of corticosterone in model mice. The eleveated level of corticosterone in plasma promote the occurrence and tumor load of colorectal cancer in mice with the normal immune system. |
PDF Full Text Request