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表没食子儿茶素没食子酸酯通过上调裸鼠Nrf2-UGT1A信号通路对原位结肠癌的抑制作用

Inhibition of epigallocatechin gallate on orthotopic colon cancer by upregulating the Nrf2-UGT1A signal pathway in nude mice.

作者信息

Yuan Jun-Hua, Li Yan-Qing, Yang Xiao-Yun

机构信息

Department of Gastroenterology, Qilu Hospital, Shandong University, Jinan, PR China.

出版信息

Pharmacology. 2007;80(4):269-78. doi: 10.1159/000106447. Epub 2007 Jul 26.

Abstract

Epigallocatechin gallate (EGCG), a key active ingredient in green tea, has many anti-carcinogenic activities. The aim of the present study was to investigate whether EGCG could prevent the occurrence or metastases of orthotopic colon cancer and probe the underlined mechanisms. We observed the inhibition of EGCG on growth and metastases of colon tumor implanted orthotopically in the cecum of nude mice. Immunohistochemistry and Western-blotting analysis were used to detect NF-E2-related factor 2 (Nrf2) protein expressions. RT-PCR was also applied to detect the mRNA levels of Nrf2, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 1A, UGT1A8 and UGT1A10 in colon tumors. As a result, the inhibition rates on tumor growth in the 3 EGCG groups were significantly different (all p < 0.001) compared with the control group. In addition, different doses of EGCG were able to inhibit liver and pulmonary metastases to varying degrees. The protein level of Nrf2 and the mRNA levels of Nrf2, UGT1A, UGT1A8 and UGT1A10 significantly increased in EGCG-treated mice in comparison with the control group (all p < 0.01). The results demonstrated that EGCG has a preventive effect on the growth and liver and pulmonary metastases of orthotopic colon cancer in nude mice, and this anticancer effect could be partly caused by activating the Nrf2-UGT1A signal pathway.

摘要

表没食子儿茶素没食子酸酯(EGCG)是绿茶中的关键活性成分,具有多种抗癌活性。本研究的目的是探讨EGCG是否能预防原位结肠癌的发生或转移,并探究其潜在机制。我们观察了EGCG对裸鼠盲肠原位植入的结肠肿瘤生长和转移的抑制作用。采用免疫组织化学和蛋白质印迹分析检测核因子E2相关因子2(Nrf2)蛋白表达。还应用逆转录-聚合酶链反应(RT-PCR)检测结肠肿瘤中Nrf2、尿苷5'-二磷酸葡萄糖醛酸基转移酶(UGT)1A、UGT1A8和UGT1A10的mRNA水平。结果显示,与对照组相比,3个EGCG组的肿瘤生长抑制率均有显著差异(均p<0.001)。此外,不同剂量的EGCG均能不同程度地抑制肝转移和肺转移。与对照组相比,EGCG处理组小鼠的Nrf2蛋白水平以及Nrf2、UGT1A、UGT1A8和UGT1A10的mRNA水平均显著升高(均p<0.01)。结果表明,EGCG对裸鼠原位结肠癌的生长及肝转移和肺转移具有预防作用,且这种抗癌作用可能部分是由激活Nrf2-UGT1A信号通路所致。

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