Liu Lifeng, Hou Lei, Gu Shanzhi, Zuo Xiaoxiao, Meng Du, Luo Minna, Zhang Xiaojin, Huang Shangke, Zhao Xinhan
Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
Oncol Rep. 2015 Jan;33(1):297-303. doi: 10.3892/or.2014.3555. Epub 2014 Oct 20.
Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has been shown to inhibit proliferation in various types of tumors. However, few studies concerning the role and mechanism of EGCG in esophageal squamous cell carcinoma are available. Therefore, the antitumor mechanism of EGCG needs to be investigated. The present study aimed to examine the antitumor effect of EGCG on the human esophageal squamous cell carcinoma cell lines, Eca-109 and Te-1, in vitro and in vivo. Cell viability was assessed using the MTT assay and tumor formation and growth in murine xenograft models with or without EGCG treatment. Cell cycle analysis and levels of reactive oxygen species (ROS) were detected using flow cytometry. Apoptosis was measured by Annexin/propidium iodide staining. Caspase-3 cleavage and vascular endothelial growth factor (VEGF) expression were detected using western blot analysis and immunohistochemistry in tumor cell lines and tumor xenografts, respectively. The results showed that EGCG inhibited proliferation in the Eca-109 and Te-1 cells in a time- and dose-dependent manner. Tumor cells were arrested in the G1 phase and apoptosis was accompanied by ROS production and caspase-3 cleavage. In a mouse model, EGCG significantly inhibited the growth of Eca-109 tumors by increasing the expression of cleaved-caspase-3 and decreasing VEGF protein levels. Taken together, the results suggest that EGCG inhibits proliferation and induces apoptosis through ROS production, caspase-3 activation, and a decrease in VEGF expression in vitro and in vivo. Furthermore, EGCG may have future clinical applications for novel approaches to treat esophageal squamous cell carcinoma.
表没食子儿茶素-3-没食子酸酯（EGCG）是绿茶中的主要多酚类物质，已被证明可抑制多种类型肿瘤的增殖。然而，关于EGCG在食管鳞状细胞癌中的作用和机制的研究却很少。因此，需要对EGCG的抗肿瘤机制进行研究。本研究旨在检测EGCG在体外和体内对人食管鳞状细胞癌细胞系Eca-109和Te-1的抗肿瘤作用。使用MTT法评估细胞活力，并在有或无EGCG处理的小鼠异种移植模型中观察肿瘤形成和生长情况。使用流式细胞术检测细胞周期分析和活性氧（ROS）水平。通过膜联蛋白/碘化丙啶染色检测细胞凋亡。分别使用蛋白质免疫印迹分析和免疫组织化学检测肿瘤细胞系和肿瘤异种移植中的半胱天冬酶-3切割和血管内皮生长因子（VEGF）表达。结果表明，EGCG以时间和剂量依赖性方式抑制Eca-109和Te-1细胞的增殖。肿瘤细胞停滞在G1期，细胞凋亡伴随着ROS产生和半胱天冬酶-3切割。在小鼠模型中，EGCG通过增加切割的半胱天冬酶-3的表达和降低VEGF蛋白水平，显著抑制Eca-109肿瘤的生长。综上所述，结果表明EGCG在体外和体内通过ROS产生、半胱天冬酶-3激活以及VEGF表达降低来抑制增殖并诱导细胞凋亡。此外，EGCG在治疗食管鳞状细胞癌的新方法中可能具有未来的临床应用价值。
