(-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells
(-)-Epigallocatechin-3-gallate inhibition of Epstein-Barr virus spontaneous lytic infection involves ERK1/2 and PI3-K/Akt signaling in EBV-positive cells
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(-)-表没食子儿茶素-3-没食子酸酯对 Epstein-Barr 病毒自发裂解性感染的抑制涉及 EBV 阳性细胞中的 ERK1/2 和 PI3-K/Akt 信号传导。
DOI：
10.1093/carcin/bgs364
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发表时间：
2013-03-01
期刊：
影响因子：
4.7
通讯作者：
Cao, Ya
中科院分区：
文献类型：
--
作者：
Liu, Sufang;Li, Hongde;Cao, Ya
eb病毒（EBV）再激活进入裂解周期在EBV相关疾病的发展中起一定作用，包括鼻咽癌和淋巴瘤。在本研究中，我们研究了茶多酚(-)-表没食子儿茶素-3-没食子酸酯（EGCG）对EBV阳性细胞自发裂解感染的影响及其机制。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，在DNA、基因转录和蛋白水平上有效抑制EBV的组成性裂解感染。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对EBV自发裂解感染抑制作用的信号机制。结果表明，丝裂原活化蛋白激酶（MEK） （PD98059）和磷脂酰肌醇3-激酶[PI3-K (LY294002)]特异性抑制剂显著下调BZLF1和BMRF1基因的转录和表达，表明MEK/ERK1/2和PI3-K/Akt通路参与了EBV自发裂解循环级联反应。因此，EGCG抑制EBV自发溶性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。
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.