Cancer Research Institute, Xiangya School of Medicine, Central South University, Key Laboratory for Cancer and Invasion of Ministry of Education, Changsha, Hunan 410078, China.
Carcinogenesis. 2013 Mar;34(3):627-37. doi: 10.1093/carcin/bgs364. Epub 2012 Nov 24.
Epstein-Barr virus (EBV) reactivation into the lytic cycle plays certain roles in the development of EBV-associated diseases, including nasopharyngeal carcinoma and lymphoma. In this study, we investigated the effects of the tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) on EBV spontaneous lytic infection and the mechanism(s) involved in EBV-positive cells. We found that EGCG could effectively inhibit the constitutive lytic infection of EBV at the DNA, gene transcription and protein levels by decreasing the phosphorylation and activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt. By using cellular signaling pathway-specific inhibitors, we also explored the signaling mechanisms underlying the inhibitory effects of EGCG on EBV spontaneous lytic infection in cell models. Results show that specific inhibitors of Mitogen-Activated Protein Kinase Kinase (MEK) (PD98059) and phosphatidylinositol 3-kinase [PI3-K (LY294002)] markedly downregulated gene transcription and expression of BZLF1 and BMRF1 indicating that the MEK/ERK1/2 and PI3-K/Akt pathways are involved in the EBV spontaneous lytic cycle cascade. Therefore, one of the mechanisms by which EGCG inhibits EBV spontaneous lytic infection appears to involve the suppression of the activation of MEK/ERK1/2 and PI3-K/Akt signaling.
EBV 病毒（EBV）重新激活进入裂解周期在 EBV 相关疾病的发展中起着一定的作用，包括鼻咽癌和淋巴瘤。在这项研究中，我们研究了茶多酚（-）-表没食子儿茶素-3-没食子酸酯（EGCG）对 EBV 自发性裂解感染的影响及其在 EBV 阳性细胞中的作用机制。我们发现 EGCG 可以通过降低细胞外信号调节激酶 1/2（ERK1/2）和 Akt 的磷酸化和激活，有效地抑制 EBV 的组成性裂解感染，在 DNA、基因转录和蛋白水平上。通过使用细胞信号通路特异性抑制剂，我们还在细胞模型中探索了 EGCG 抑制 EBV 自发性裂解感染的信号机制。结果表明，丝裂原活化蛋白激酶激酶（MEK）（PD98059）和磷脂酰肌醇 3-激酶[PI3-K（LY294002）]的特异性抑制剂显著下调了 BZLF1 和 BMRF1 的基因转录和表达，表明 MEK/ERK1/2 和 PI3-K/Akt 途径参与了 EBV 的自发性裂解周期级联反应。因此，EGCG 抑制 EBV 自发性裂解感染的机制之一似乎涉及抑制 MEK/ERK1/2 和 PI3-K/Akt 信号的激活。
