文章：

钙、维生素D和叶酸对结肠癌的化学预防：分子机制

Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms

原文发布日期：2003-08-01

DOI: 10.1038/nrc1144

类型: Review Article

开放获取: 否

要点：

1. Colorectal cancer is one of the main causes of cancer mortality in Western societies.
2. Experimental, epidemiological and clinical evidence show that diets consumed by Western populations have an important role in the modulation of this disease.
3. Calcium, vitamin D and folate have emerged as promising chemopreventive agents in colon cancer.
4. One of the main pathways used by extracellular calcium to exert its chemopreventive actions is through activation of a calcium-sensing receptor. This results in increased levels of intracellular calcium, inducing a wide range of biological effects, some of which restrain the growth and promote the differentiation of transformed colon cells.
5. Most of the pleiotropic actions of vitamin D are mediated by binding to a nuclear receptor, which interacts with specific consensus sites in promoters of specific genes, resulting in downregulation or upregulation of their expression. The actions of vitamin D involve cross-talk with growth factors/cytokines, inhibitory effects on the cell cycle and stimulation of apoptosis.
6. Folate lies at the intersection of metabolic pathways involved in DNA methylation and biosynthesis. Three main mechanisms by which decreased levels of folate (and of other dietary one-carbon donors) might increase the risk of cancer are: alteration of the normal DNA-methylation process; imbalance of the steady-state level of DNA precursors, leading to aberrant DNA synthesis and repair; and chromosome and chromatin changes.
7. It is proposed that, together with the application of genome methodology to elucidate nutrient–gene interactions, a deliberate effort should be made to identify nutrient-induced key events in signal-transduction pathways and in the cell cycle that are involved either in the chemoprevention or promotion of colorectal cancer.

要点翻译：

1. 结直肠癌是西方社会癌症死亡率的主要原因之一。
2. 实验、流行病学和临床证据表明，西方人群的饮食在调节该疾病中起着重要作用。
3. 钙、维生素D和叶酸已成为结肠癌中有前景的化学预防剂。
4. 细胞外钙发挥其化学预防作用的主要途径之一是通过激活钙敏感受体。这导致细胞内钙水平升高，诱导广泛的生物学效应，其中一些效应抑制转化结肠细胞的生长并促进其分化。
5. 维生素D的多效作用大多通过与其核受体结合来介导，该受体与特定基因启动子中的特定共识位点相互作用，从而下调或上调其表达。维生素D的作用涉及与生长因子/细胞因子的交叉对话、对细胞周期的抑制效应以及刺激细胞凋亡。
6. 叶酸处于DNA甲基化和生物合成代谢途径的交叉点。叶酸（及其他膳食一碳供体）水平降低可能增加癌症风险的三个主要机制是：改变正常的DNA甲基化过程；破坏DNA前体稳态水平，导致异常的DNA合成和修复；以及染色体和染色质变化。
7. 建议在应用基因组方法阐明营养素-基因相互作用的同时，应有意识地努力识别营养素在信号转导通路和细胞周期中诱导的关键事件，这些事件参与结直肠癌的化学预防或促进。

英文摘要：

Recent findings have indicated that dietary calcium, vitamin D and folate can modulate and inhibit colon carcinogenesis. Supporting evidence has been obtained from a wide variety of preclinical experimental studies, epidemiological findings and a few human clinical trials. Important molecular events and cellular actions of these micronutrients that contribute to their tumour-modulating effects are discussed. They include a complex series of signalling events that affect the structural and functional organization of colon cells.

摘要翻译： 

最新研究发现，膳食中的钙、维生素D和叶酸可调节并抑制结肠癌的发生。这一结论得到了大量临床前实验、流行病学证据以及少数人体临床试验的支持。文章讨论了这些微量营养素发挥肿瘤调节作用的关键分子事件与细胞机制，包括一系列复杂的信号传导过程，这些过程影响结肠细胞的结构与功能组织。

原文链接：

Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms