Effects of Folate and Choline Nutrient Status on tumor microenvironment and energy metabolism in Colitis Associated Colorectal Cancer

Autor: Gu, Yu-Ting, 古育婷
Rok vydání: 2019
Druh dokumentu: 學位論文 ; thesis
Popis: 107
The energy metabolism of tumor cells is different from the normal cells. Whether or not there is sufficient oxygen, tumor cells convert glucose into lactate. This metabolic pathway is Warburg effect. The tumor cells can rapidly generate much energy by Warburg effect, and lactate releases outside the cell can be a microenvironment that promotes the proliferation and metastasis. Studies have shown that the malnutrition in methyl-related and colitis predisposed CRC and cancer cells metastasis. The effect of folate and choline nutrient status on the mechanism of energy in CRC (colorectal cancer) remain unclear. Therefore, the aim of this study is to investigate folate and choline nutrient status regulates lactate metabolism and tumor microenvironment in CAC (colitis-associated colorectal cancer) mice. The C57BL/6 mice grouping as control group, low folate diet group (LF), low folate/low choline group (LFLC) and folate supplement group (SF). The mice to establish CAC model by treated azoxymethane (AOM) and dextran sulfate sodium (DSS) after three weeks. Finally, i.p. injected highly metastatic lewis lung carcinoma cell. The results showed that all groups induced colon cancer and metastasized to liver and spleen. There were no significant differences in the number and size of colon, liver and spleen tumors. There were the largest colon tumors in LFLC group; the smallest colon tumor in SF group. The serum folate and colon tissues folate were significantly lower in the LF and LFLC groups than the control and SF groups. The colon tumor folate was significantly lower in the LF group than in the Control and SF groups. The lactate accumulation in colon tumors showed that the LF and SF group were significantly higher than the Control group. The folate concentration in the pair colon tissues was significantly negative correlation with the lactate accumulation in the tumors (r=-0.370, P=0.037). There was a significant negative correlation between serum folate concentration and NADH concentration in colon tumors (r=-0.622, P=0.0001) and pair colon tissues (r=-0.335, P=0.046). There was a significant negative correlation between NADH concentration and pair tumor tissues (r=-0.335, P=0.046). There was a significant negative correlation between colon folate concentration and NADH concentration in colon tumors (r=-0.543, P=0.0013). There was a significant negative correlation between lactate accumulation in pair tumor tissues and NADH concentration in tumors (r=-0.398, P=0.024). There was a significant positive correlation between serum folate concentration and NADPH concentration in colon tumors (r=0.844, P
Databáze: Networked Digital Library of Theses & Dissertations
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