Green tea polyphenols inhibit colorectal aberrant crypt foci (ACF) formation and prevent oncogenic changes in dysplastic ACF in azoxymethane-treated F344 rats
Green tea polyphenols inhibit colorectal aberrant crypt foci (ACF) formation and prevent oncogenic changes in dysplastic ACF in azoxymethane-treated F344 rats
复制标题
绿茶多酚抑制氧化偶氮甲烷处理的 F344 大鼠结直肠异常隐窝病灶 (ACF) 形成并预防发育不良 ACF 的致癌变化
DOI：
10.1093/carcin/bgm204
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发表时间：
2008-01-01
期刊：
影响因子：
4.7
通讯作者：
Yang, Chung S.
中科院分区：
文献类型：
--
作者：
Xiao, Hang;Hao, Xingpei;Yang, Chung S.
绿色茶及其成分在许多动物模型中显示出预防癌症的活性。为了准备人体试验对结肠癌的抑制作用，我们进行了研究与绿色茶多酚作为预防剂在氧化偶氮甲烷（AOM）诱导的大鼠结肠癌模型，以异常隐窝灶（ACF）为终点。F344大鼠每周两次注射AOM（15 mg/kg），然后喂食含有或不含0.12或0.24% Polyphenon E（PPE，一种标准化的绿色茶制剂，由65%的（-）-表没食子儿茶素-3-没食子酸酯和22%的其它儿茶素组成）的20%高脂肪饮食8周。亚甲基蓝染色后，在显微镜下分析结直肠ACF。发现膳食PPE给药可显著且剂量依赖性地降低每只大鼠的ACF总数和每只大鼠的异常隐窝总数。此外，用0.24%PPE处理还显著降低了大ACF（四个或更多隐窝）的百分比和具有高度异型增生的ACF在总ACF中的百分比。0.24%PPE处理组的高度异型增生ACF细胞凋亡增加，β-连环蛋白和细胞周期蛋白D1的核表达水平降低。在AOM诱导的结肠癌发生过程中，高度异型增生ACF、腺瘤和腺癌中维甲酸X受体（RXR）α表达降低，PPE治疗部分防止了高度异型增生ACF中RXR α表达的丧失。总之，我们的研究结果强烈表明PPE的结肠癌预防活性，并确定了未来结肠癌预防研究的可能分子标志物。
Green tea and its constituents have shown cancer-preventive activities in many animal models. In order to prepare for a human trial on the inhibition of colon carcinogenesis, we conducted a study with green tea polyphenols as the preventive agent in an azoxymethane (AOM)-induced rat colon cancer model using aberrant crypt foci (ACF) as an end point. F344 rats were given two weekly injections of AOM (15 mg/kg), and then fed a 20% high-fat diet with or without 0.12 or 0.24% Polyphenon E (PPE, a standardized green tea preparation consisting 65% of (-)-epigallocatechin-3-gallate and 22% of other catechins) for 8 weeks. Colorectal ACF were analyzed under a microscope after methylene blue staining. Dietary PPE administration was found to significantly and dose dependently decrease the total number of ACF per rat and the total number of aberrant crypt per rat. Moreover, treatment with 0.24% PPE also significantly decreased the percentage of large ACF (four or more crypts) and the percentage of ACF with high-grade dysplasia in total ACF. The high-grade dysplastic ACF from 0.24% PPE-treated group had increased apoptosis and decreased nuclear expression levels of beta-catenin and cyclin D1. Retinoid X receptor (RXR)alpha expression was reduced in high-grade dysplastic ACF, adenoma and adenocarcinoma during AOM-induced colon carcinogenesis, and the PPE treatment partially prevented the loss of RXR alpha expression in high-grade dysplastic ACF. Taken together, our results strongly suggest the colon cancer-preventive activity of PPE and identified possible molecular markers for future colon cancer prevention studies.