高油飲食中添加含Betanin蔬果對受Azoxymethane與Dextran Sulfate Sodium誘發小鼠大腸發炎及大腸癌之影響

Abstract

Cancer was the top cause leading to death in 2008, and colorectal cancer ranked the third among the cancers (Department of Health, Executive Yuan, Taiwan). Diet has been considered to affect the morbidity and mortality of colorectal cancer, and the results of epidemiological studies also suggest that intake of varieties of vegetables and fruits may reduce the risk of suffering cancers. In addition to dietary fiber, fruits and vegetables also provide secondary metabolites which may have the potential to promote human health. Among them, the anticarcinogen effect of betanin had been confirmed in cell culture study. However, the effects of health promoting on gastrointestinal system in living stocks has not yet been focused. The objective of this study was to study the effect of betanin containing vegetables and fruits in high fat diet on colon inflammation and cancer on ICR mouse. The animal experimental model of inducing colon cancer on ICR mouse we used was by injecting azoxymethane (AOM) as carcinogen and adding dextran sulfate sodium (DSS) in drinking water as acute inflammatory agent. The basal high fat medium (HF) was modified from AIN-93 by increasing the fat content to 30%. By adding 10% (w/w) of 3 betanin containing plant tissues, 3 feeds were provided as following: red pitaya fruit pulp containing feed (HFPU), red pitaya fruit peel containing feed (HFPE) and beetroot containing feed (HFB). Adding 10% (w/w) head lettuce to the HF basal medium and providing 0.0025% betanin in drinking water was designed as HFS. HF medium along was as control. AOM injection did not cause death or affect mouse’s activity and growing. Drinking DSS containing water induced acute intestinal inflammation and caused death. The survival rate decreased in the mouse feeding when pitaya (peel and plup) and beetroots were added to the HF medium; however, the survival rate increased when head lettuce and betanin containing drinking water was provided. The survived mouse were sacrificed after 15 weeks for the analyses of immunohistochemistry staining, pathological sections, expression levels of anti-inflammatory and cancer-associated gene in colorectal tissue. High fat diet along did not significantly affected the intestinal oxidative stress and the expression of Nrf2, Ki-67, c-Myc and c-Myb. However, all of them were increased after the AOM and DSS application, and intestinal proliferation was resulted. Adding betanin containing fruits and vegetables to high fat diet reduced Nrf2, Ki-67 and c-Myb expression but increased expression of Cox2 and c-Myc in the intestine of AOM-DSS treated mouse. The alteration in the expression of anti-inflammatory and intestinal proliferation genes might contribute to the severity of intestinal proliferation and inflammation. After long-term inflammation, tumors might appear in colon tissue. Tumor-related analysis further confirmed that adding betanin to high fat diet might increase the morbidity of colon tumor under the caner inducing model. Therefore, we concluded that betanin containing fruits and vegetables are not suggested while intestine is inflamming. However, the effects of health promoting on gastrointestinal system on normal mouse was not studied in this thesis.