The Regulatory Role of Methyl-related Nutrients Intake in Colitis Associated Colorectal Cancer Metastases

• Main Authors: Hong-Jun Yu Chi, 尉遲浤圳
• Other Authors: Rwei Fen Syu Huang
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/16082426111913494037

碩士 === 輔仁大學 === 營養科學系碩士班 === 103 === Folic acid has been associated with sporadic and inflammation-mediated colon cancer. Dietary folate intake and folate status have been associated with protection from UC-associated CRC. Low folate status is well recognized as one of the metabolic stressors for colorectal cancer carcinogenesis, but its role in colon cancer metastasis remains unknown. Some epidemiologic studies have evaluated the association of dietary choline and betaine intakes with some types of cancers. Aberrant DNA methylation is an early event in colorectal carcinogenesis and is typically associated with the transcriptional silencing of tumour suppressor genes. The aims of this study were to investigate whether and how methyl-related nutrients status and inflammation affect invasion and metastasis by CRC in association with EMT, Shh signaling and the NF-κB pathway. And clarify whether methylation status of related molecules may play an important role in above mechanism. We used 6 weeks C57BL/6 mice as Control group (C), Low folate diet group (LF) (0.5mg folate/kg diet), Low folate/low choline group(LFLC) (0.5mg folate/kg diet; 1.25g choline/kg diet) and folate supplement group (SF) (folic acid drinking water 0.03mg/ml as supplement). Mice were treated 1.5% DSS in water, AOM (25mg/ml) by i.p injection and lewis lung carcinoma (LLC) cell (1x106 cells) by i.p injection to establish colitis associated colorectal cancer model. However, we found that both LF and SF diet mice increased colitis level. In addition, both LF and SF diet mice also increased the invasion and metastasis of colitis associated colorectal cancer. On the other hand, that the percentage of spleen tumor size >3mm were significantly increased in LFLC diet mice. We also investigated whether methyl-related nutrients status and inflammation affect CRC progression and aggressiveness in association with EMT, Shh signaling and the NF-κB pathway. Our data indicated that folate supplement affect EMT signaling pathway associated protein expression. In summary, methyl-related nutrients affect inflammation level of colitis and progression of CRC.