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(-)-表没食子儿茶素-3-没食子酸酯通过抑制Wnt/β-连环蛋白信号通路抑制结直肠癌干细胞

(-)-Epigallocatechin-3-Gallate Inhibits Colorectal Cancer Stem Cells by Suppressing Wnt/β-Catenin Pathway.

作者信息

Chen Yue, Wang Xiao-Qian, Zhang Qi, Zhu Jian-Yun, Li Yuan, Xie Chun-Feng, Li Xiao-Ting, Wu Jie-Shu, Geng Shan-Shan, Zhong Cai-Yun, Han Hong-Yu

机构信息

Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.

出版信息

Nutrients. 2017 Jun 3;9(6):572. doi: 10.3390/nu9060572.

Abstract

The beneficial effects of tea consumption on cancer prevention have been generally reported, while (-)-Epigallocatechin-3-gallate (EGCG) is the major active component from green tea. Cancer stem cells (CSCs) play a crucial role in the process of cancer development. Targeting CSCs may be an effective way for cancer intervention. However, the effects of EGCG on colorectal CSCs and the underlying mechanisms remain unclear. Spheroid formation assay was used to enrich colorectal CSCs from colorectal cancer cell lines. Immunoblotting analysis and quantitative real-time polymerase chain reaction were used to measure the alterations of critical molecules expression. Immunofluorescence staining analysis was also used to determine the expression of CD133. We revealed that EGCG inhibited the spheroid formation capability of colorectal cancer cells as well as the expression of colorectal CSC markers, along with suppression of cell proliferation and induction of apoptosis. Moreover, we illustrated that EGCG downregulated the activation of Wnt/β-catenin pathway, while upregulation of Wnt/β-catenin diminished the inhibitory effects of EGCG on colorectal CSCs. Taken together, this study suggested that EGCG could be an effective natural compound targeting colorectal CSCs through suppression of Wnt/β-catenin pathway, and thus may be a promising agent for colorectal cancer intervention.

摘要

一般报道称饮茶对预防癌症有益,而(-)-表没食子儿茶素-3-没食子酸酯(EGCG)是绿茶中的主要活性成分。癌症干细胞(CSCs)在癌症发展过程中起关键作用。靶向癌症干细胞可能是一种有效的癌症干预方法。然而,EGCG对结直肠癌干细胞的影响及其潜在机制仍不清楚。采用球体形成试验从结直肠癌细胞系中富集结直肠癌干细胞。免疫印迹分析和定量实时聚合酶链反应用于检测关键分子表达的变化。免疫荧光染色分析也用于确定CD133的表达。我们发现,EGCG抑制了结直肠癌细胞的球体形成能力以及结直肠癌干细胞标志物的表达,同时抑制细胞增殖并诱导凋亡。此外,我们还表明,EGCG下调了Wnt/β-连环蛋白通路的激活,而Wnt/β-连环蛋白的上调则减弱了EGCG对结直肠癌干细胞的抑制作用。综上所述,本研究表明,EGCG可能是一种通过抑制Wnt/β-连环蛋白通路靶向结直肠癌干细胞的有效天然化合物,因此可能是一种有前景的结直肠癌干预药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c40/5490551/a01b6be66a2e/nutrients-09-00572-g001.jpg

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