EBV裂解活化与鼻咽癌放疗抗性的分子机制研究

EBV是重要的致瘤病毒。EBV裂解活化在EBV阳性肿瘤的发生发展以及治疗抗性中具有重要的意义。本项目以我们实验室的前期主要科学发现为基础，围绕本研究领域的国际进展，拟集中探讨EBV编码的致瘤蛋白LMP1在调节病毒裂解活化中的新功能，研究EGCG靶向LMP1抑制病毒裂解活化对改进肿瘤放疗抗性的新机制：1.确定LMP1对EBV裂解活化的调控，拓展对LMP1的新认识；2.探讨LMP1作为EGCG分子靶标的可能性，发现LMP1介导的细胞氧化应激在EBV裂解活化中的新机理；3.提出EGCG靶向LMP1降低氧化应激，抑制EBV裂解活化，增加放疗敏感性的新证据，为EBV阳性肿瘤治疗提供新的思路。

EBV is an important oncovirus. EBV reactivation is highly significant in the pathogenesis of EBV-related diseases, which are closely related with patient survival and clinical stage of EBV-related cancers. Recent research suggested that the EBV encoded oncoprotein LMP1 might play an important role in EBV lytic activation. This project will investigate the novel function of LMP1 in EBV lytic activation and determine the role of oxidative stress mediated by LMP1 in EBV lytic reactivition. We will explore the possibility that EGCG directly targets EBV LMP1 and inhibits EBV lytic activation, which will establish a new relationship between blocking EBV lytic activation and increased radio sensitivity. These innovative studies will expand and provide new evidence showing that EBV lytic reactivation contributes to oncogenesis and therapeutic resistance in EBV-related tumors, and will identify a new function of LMP1 in the regulation of EBV lytic reactivition. This will provide more novel experimental evidence for EBV-related cancer treatment in the near future.