S-adenosyl L-methionine inhibits azoxymethane-induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco-2 cell growth in 3D culture
S-adenosyl L-methionine inhibits azoxymethane-induced colonic aberrant crypt foci in F344 rats and suppresses human colon cancer Caco-2 cell growth in 3D culture
复制标题
DOI：
10.1002/ijc.23031
复制
发表时间：
2008-01-01
影响因子：
6.4
通讯作者：
Rao, Chinthalapally V.
中科院分区：
文献类型：
--
作者：
Guruswamy, Suresh;Swamy, Malisetty V.;Rao, Chinthalapally V.
S-腺苷甲硫氨酸（SAM）是各种中间代谢物、激素、蛋白质、神经递质、磷脂和核酸的通用甲基供体。叶酸在SAM合成中起作用，叶酸缺乏会导致结肠癌风险增加。本研究测试了SAM补充剂在保护雄性F344大鼠免受氧化偶氮甲烷诱导的结肠癌发生方面的有效性。我们还测试了SAM对巨噬细胞系中环氧合酶-2（考克斯-2）的影响。此外，我们使用Caco-2细胞开发了一个3-D培养模型，以测试SAM对肿瘤球体大小和数量的影响。各组大鼠在第一次AOM注射前1周给予含有0-、400-或800-ppm SAM的实验饮食，并持续至8周。在对照组中，AOM产生大量异常隐窝病灶（ACF）（96 +/- 8）。SAM的饮食施用显著降低了总ACF的数量（400 ppm SAM，68 +/- 7.3，p < 0.01和800 ppm SAM，57 +/- 7.1，p < 0.001）。SAM以剂量依赖性方式显著减少AOM诱导的结肠多密病灶。在RAW264.7细胞系中观察到脂多糖（LPS）诱导的考克斯-2蛋白表达的抑制。我们建立了Caco-2细胞作为球状体在胶原蛋白和基质胶的3D基质中的生长。SAM处理以剂量依赖性方式降低球状体的大小和数量（p < 0.0001）。这些观察结果首次证明SAM可以减少AOM处理的雄性F344大鼠中ACF的发生，并抑制人肿瘤球体的形成和考克斯-2的表达。(C)2007 Wiley-Liss，Inc.
S-Adenosyl L-methionine (SAM) is a universal methyl group donor to various intermediary metabolites, hormones, proteins, neurotransmitters, phospholipids and nucleic acids. Deficiency of folate, which plays a role in the synthesis of SAM leads to increased risk for colon cancer. This study tested the effectiveness of SAM supplementation in protecting against azoxymethane induced colon carcinogenesis in male F344 rats. We also tested the effect of SAM on cyclooxygenase-2 (COX-2) in a macrophage cell line. Further, we developed a 3-D culture model using Caco-2 cells to test the effect of SAM on tumor spheroid size and number. Groups of rats were given the experimental diet containing either 0-, 400- or 800-ppm SAM, 1 week before the first AOM injection and continued until 8 weeks. In the control group, AOM produced a substantial number of aberrant crypt foci (ACF) (96 +/- 8). Dietary administration of SAM significantly reduced the number of total ACF (400 ppm SAM, 68 +/- 7.3, p < 0.01 and 800 ppm SAM, 57 +/- 7.1, p < 0.001). SAM significantly decreased AOM-induced colonic multicrypt foci in a dose-dependent manner. Suppression of Lipopolysaccharide (LPS) induced COX-2 protein expression was observed in a RAW264.7 cell line. We established growth of Caco-2 cells as spheroids, in a 3D matrix of collagen and matrigel. Treatment with SAM decreased both size and number of spheroids in a dose-dependent manner (p < 0.0001). These observations demonstrate for the first time that SAM can reduce, the occurrence of ACF in AOM treated male F344 rats and suppress formation of human tumor spheroids and expression of COX-2. (C) 2007 Wiley-Liss, Inc.