Tea Modulation of Colon Carcinogenesis

描述（由申请人提供）：绿色茶和红茶一起代表了全世界最常消费的饮料，并且是具有广泛的抗癌化学预防活性的植物化学物质的极少数来源之一。这种活性和缺乏毒性使茶成为潜在用于降低人类癌症风险的有吸引力的试剂。食用绿色茶可以降低患肺癌、胃癌和胰腺癌等多种癌症的风险。最近有研究表明，习惯性喝茶与美国人群中结肠癌的风险降低有关。然而，在我们完全了解茶的癌症化学预防活性以及茶在人类癌症预防中的可能应用之前，还需要更多的研究。该项目的总体目标是通过阐明机制和识别所涉及的活性成分来了解茶和癌症预防。将使用结肠癌和相关细胞系的Apc Min/+小鼠动物模型。该项目将开发有用的生物标志物，新药物（活性成分的代谢物或类似物）和有效的预防人类癌症的剂型。具体来说，我们打算测试的假设，口服茶是一种有效的抑制致癌作用。Min小鼠和氧化偶氮甲烷（AOM）处理的Min小鼠将被用作动物模型，以进行茶叶对异常隐窝病灶和结肠肿瘤形成的影响的剂量反应研究。将评估绿色茶和红茶之间的可能差异以及咖啡因对结肠肿瘤发生的影响。我们接下来将确定绿色茶和红茶对结肠细胞增殖和凋亡的影响，并将其与肿瘤发生结果相关联。为了研究分子机制，将测试茶调节Min小鼠结肠中的AP-1、ERK、JNK、c-Jun、β-连环蛋白和其它蛋白质的能力。为了阐明绿色茶和红茶在Min和AOMIM小鼠模型中抑制结肠turnorigenesis的机制基础，将用结肠样品进行花生四烯酸代谢、环氧合酶（考克斯）蛋白和mRNA水平以及考克斯、脂氧合酶和磷脂酶A2的活性的研究。此外，将进行检查茶多酚对具有高水平考克斯-2表达的人结肠腺癌细胞的生长的影响的研究。

DESCRIPTION (provided by applicant): Green and black tea together represent the most commonly consumed beverages worldwide and is one of very few sources of phytochemicals with a broad chemopreventive activity against carcinogenesis. This activity and the lack of toxicity make tea an attractive agent for potential use in the reduction of human cancer risk. Consumption of green tea reduces risk for several cancers including lung, stomach, and pancreatic cancer. Recently it has been shown that habitual consumption of tea is associated with a reduced risk for colon cancer in a U.S. population. Nevertheless, much more research is needed before we can fully understand the cancer chemopreventive activities of tea and the possible application of tea in human cancer prevention. The overall goal of this project is to understand tea and cancer prevention by elucidating the mechanisms and identifying the active components involved. The Apc Min/+ mouse animal model for colon cancer and related cell lines will be used. This project will develop useful biomarkers, new agents (metabolites or analogs of the active components), and effective dosage forms for the prevention of human cancer. Specifically, we intend to test the hypothesis that orally administered tea is an effective inhibitor of carcinogenesis. The Min mouse and azoxymethane (AOM)-treated Min mouse will be used as the animal models to conduct dose-response studies for the effect of tea on aberrant crypt foci and colon tumor formation. Possible differences between green tea and black tea and the effect of caffeine on colon tumorigenesis will be assessed. We next will determine the effect of green tea and black tea on the proliferation and apoptosis of cells in the colon and correlate it with the tumorigenesis results. To study the molecular mechanisms, tea will be tested for its ability to modulate AP-l, ERK, JNK, c-Jun, j3-catenin and other proteins in the colons of Min mice. To elucidate the mechanistic basis for the inhibition of colon turnorigenesis by green tea and black tea in the Min and AOMIMin mouse models studies on arachidonic acid metabolism, cyclooxygenase (COX) protein and mRNA levels, and activities of COX, lipoxygenase, and phospholipase A2 will be conducted with colon samples. Furthermore, studies examining the effect of tea polyphenols on the growth of human colon adenocarcinoma cells that have high levels of COX-2 expression will be conducted.