Huaihe Hospital, Henan University, Kaifeng 475000, P.R. China.
Oncol Rep. 2013 Dec;30(6):2691-6. doi: 10.3892/or.2013.2743. Epub 2013 Sep 20.
Signal transducer and activator of transcription 3 (STAT3) is an oncogene that promotes cell survival, proliferation, and motility. In the present study, we explored the mechanism involved in the inhibition by epigallocatechin-3-gallate (EGCG) of STAT3 signaling as detected by surface plasmon resonance (SPR)-binding assays and in silico docking. Stat3‑binding assay indicated that EGCG significantly interrupted Stat3 peptide binding at micromolar concentrations, and the docking experiments indicated that EGCG had a strong interaction with Arg-609, one of the key residues in the STAT3 SH2 domain that contributes greatly to Stat3 and phosphorylated peptide binding. Following treatment of the hepatocellular carcinoma cell lines BEL-7402 and QGY-7703 with EGCG, in vitro, EGCG significantly suppressed cell proliferation as detected by MTT assay, induced apoptosis as detected by flow cytometry, dramatically lowered the expression levels of phosphorylated Stat3 proteins (p-Stat3) as determined by immunoblot detection, and inhibited the expression of multiple genes including Bcl-xL, c-Myc, VEGF and cyclin D1 as demonstrated by RT-PCR analysis. In conclusion, our research data indicate that the anticancer function of green tea results from the inhibition of the STAT3 signaling pathway by EGCG.
信号转导子和转录激活因子 3（STAT3）是一种致癌基因，可促进细胞存活、增殖和迁移。在本研究中，我们通过表面等离子体共振（SPR）结合分析和计算机对接实验探索了 EGCG 抑制 STAT3 信号通路的机制。Stat3 结合实验表明，EGCG 在微摩尔浓度下可显著中断 Stat3 肽的结合，对接实验表明，EGCG 与 STAT3 SH2 结构域中的关键残基之一 Arg-609 具有很强的相互作用，Arg-609 对 Stat3 和磷酸化肽的结合有很大贡献。在体外使用 EGCG 处理肝癌细胞系 BEL-7402 和 QGY-7703 后，MTT 检测表明 EGCG 显著抑制细胞增殖，流式细胞术检测表明诱导细胞凋亡，免疫印迹检测表明磷酸化 Stat3 蛋白（p-Stat3）的表达水平显著降低，RT-PCR 分析表明多种基因的表达受到抑制，包括 Bcl-xL、c-Myc、VEGF 和 cyclin D1。综上所述，我们的研究数据表明，绿茶的抗癌功能源自 EGCG 抑制 STAT3 信号通路。
