Tea Science Institute, Zhejiang University, Hangzhou 310058, China.
Department of Nutrition, University of California, Davis, CA 95616, USA.
Nutrients. 2019 Aug 9;11(8):1856. doi: 10.3390/nu11081856.
Most pancreatic cancers are usually diagnosed at an advanced stage when they have already metastasized. Epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to reduce pancreatic cancer growth, but its effect on metastasis remains elusive. This study evaluated the capacity of EGCG to inhibit pancreatic cancer cell migration and invasion and the underlying mechanisms. EGCG reduced pancreatic cancer cell growth, migration, and invasion in vitro and in vivo. EGCG prevented "Cadherin switch" and decreased the expression level of TCF8/ZEB1, β-Catenin, and Vimentin. Mechanistically, EGCG inhibited the Akt pathway in a time-dependent manner, by suppressing IGFR phosphorylation and inducing Akt degradation. Co-treatment with catalase or N-Acetyl-L-cysteine did not abrogate EGCG's effect on the Akt pathway or cell growth. Moreover, EGCG synergized with gemcitabine to suppress pancreatic cancer cell growth, migration, and invasion, through modulating epithelial-mesenchymal transition markers and inhibiting Akt pathway. In summary, EGCG may prove beneficial to improve gemcitabine sensitivity in inhibiting pancreatic cancer cell migration and invasion, to some extent through the inhibition of Akt pathway and epithelial-mesenchymal transition.
大多数胰腺癌通常在已经转移的晚期才被诊断出来。表没食子儿茶素没食子酸酯（EGCG）是绿茶中的一种主要多酚成分，已被证明可以减少胰腺癌的生长，但它对转移的影响仍不清楚。本研究评估了 EGCG 抑制胰腺癌细胞迁移和侵袭的能力及其潜在机制。EGCG 可减少体外和体内胰腺癌细胞的生长、迁移和侵袭。EGCG 可预防“钙粘蛋白转换”，并降低 TCF8/ZEB1、β-连环蛋白和波形蛋白的表达水平。从机制上讲，EGCG 通过抑制 IGF1R 磷酸化和诱导 Akt 降解，以时间依赖性方式抑制 Akt 途径。用 Catalase 或 N-Acetyl-L-cysteine 处理并不能消除 EGCG 对 Akt 途径或细胞生长的影响。此外，EGCG 通过调节上皮-间充质转化标志物和抑制 Akt 途径，与吉西他滨协同抑制胰腺癌细胞的生长、迁移和侵袭。总之，EGCG 可能有助于提高吉西他滨抑制胰腺癌细胞迁移和侵袭的敏感性，在一定程度上通过抑制 Akt 途径和上皮-间充质转化。
