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L-茶氨酸通过下调 MMP9 和 Snail 抑制前列腺癌的转移。

L-theanine suppresses the metastasis of prostate cancer by downregulating MMP9 and Snail.

机构信息

Jiangsu Province Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University, Nanjing, Jiangsu, People's Republic of China.

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, People's Republic of China.

出版信息

J Nutr Biochem. 2021 Mar;89:108556. doi: 10.1016/j.jnutbio.2020.108556. Epub 2020 Nov 26.

DOI:10.1016/j.jnutbio.2020.108556
PMID:33249185
Abstract

Prostate cancer (PCa) is a very prevalent male-specific malignancy; most PCa patients eventually die as a result of metastasis. L-theanine (C7H14N2O3), a nonprotein amino acid derivative from green tea leaves, has been demonstrated to act as an anticarcinogen through proapoptotic and antiproliferative effects. However, the antimetastatic effect of L-theanine in tumor cells and its underlying mechanism are still unclear. Here, we found that L-theanine could suppress invasion, migration, and increase cell-cell adhesion of prostate cancer cells in vitro and in vivo. We also found that L-theanine could inhibit the epithelial-mesenchymal transition process in PCa. Our study revealed that L-theanine could downregulate MMP9, N-cadherin, Vimentin, Snail, and upregulate E-cadherin. Furthermore, L-theanine suppressed the transcription of MMP9 and Snail by significantly inhibiting the ERK/NF-κB signaling pathway and the binding activity of p65 to the promoter regions of MMP9 and Snail. All of these findings suggest that L-theanine has therapeutic potential for metastatic PCa and may be considered a promising candidate for antimetastatic therapy of prostate cancer.

摘要

前列腺癌(PCa)是一种非常普遍的男性特异性恶性肿瘤;大多数 PCa 患者最终因转移而死亡。L-茶氨酸(C7H14N2O3)是绿茶叶中的一种非蛋白氨基酸衍生物,已被证明具有通过促进细胞凋亡和抑制增殖来发挥抗癌作用。然而,L-茶氨酸在肿瘤细胞中的抗转移作用及其潜在机制尚不清楚。在这里,我们发现 L-茶氨酸可以抑制前列腺癌细胞的侵袭、迁移,并增加细胞间黏附,无论是在体外还是体内。我们还发现 L-茶氨酸可以抑制 PCa 中的上皮-间充质转化过程。我们的研究表明,L-茶氨酸可以下调 MMP9、N-钙黏蛋白、波形蛋白、Snail,上调 E-钙黏蛋白。此外,L-茶氨酸通过显著抑制 ERK/NF-κB 信号通路和 p65 与 MMP9 和 Snail 启动子区域的结合活性,抑制 MMP9 和 Snail 的转录。所有这些发现表明 L-茶氨酸具有治疗转移性 PCa 的潜力,可能被认为是前列腺癌抗转移治疗的有前途的候选药物。

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