项目以放疗敏感性不同的鼻咽癌细胞系、鼻咽癌裸鼠移植瘤以及临床鼻咽癌组织为样本，以我们前期研究识别的鼻咽癌放疗抵抗相关蛋白质为切入点，以调控细胞生长与凋亡的关键信号通路PI3K/AKT/NF-kappaB为核心，研究多分子、多位点激活PI3K/AKT/NF-kappaB信号通路在鼻咽癌放疗抵抗中的作用，即通过分析这些蛋白质表达改变对鼻咽癌细胞PI3K/AKT/NF-kappaB信号通路活性的影响及其与鼻咽癌放疗敏感性(细胞生长、凋亡、细胞周期和DNA损伤修复)的关系，阐明PI3K/AKT/NF-kappaB信号通路异常活化在鼻咽癌放疗抵抗中的作用，从我们识别的鼻咽癌放疗抵抗相关蛋白中发现关键的鼻咽癌放疗抵抗分子。项目研究成果不仅有助于揭示鼻咽癌放疗抵抗的分子机制，而且能为鼻咽癌放疗增敏、靶向治疗、药物研发以及放疗敏感性预测提供靶标。

To elucidate the molecular mechanisms of nasopharyngeal carcinoma (NPC) radioresistance, in this project we will use NPC cell lines, NPC xenografts and clinical NPC tissues with different radiosensitivity as a study sample, use NPC radioresistance-related proteins previously identified by us as a study subject, use prosurvival PI3K/AKT/NF-kappaB signaling pathway as a study focus, and investigate the roles and mechanisms of PI3K/AKT-NF-kappaB signaling pathway regulated by multimolecule and multilayer in the NPC radioresistance. We will modulate the expressional levels of these radioresistance-related proteins in NPC cells using transfection techniques, analyze the effects of these proteins expressional changes on NPC PI3K/AKT/NF-kappaB signaling pathway activity and NPC radiosensitivity such as growth, apoptosis, cell cycle and DNA repair, and determine the relation between the changes of PI3K/AKT/NF-kappaB signaling pathway activity and NPC radiosensitivity, which can elucidate the roles of abnormally activating PI3K/AKT/NF-kappaB signaling pathway in NPC radioresistance, and descover the key mediated-NPC radioresistant molecules from our previously identified NPC radioresistance-related proteins. Our expected data will not only be helpful to reveal the molecular mechanisms of NPC radioresistance, but also can provide novel targets for radiosensitization, targeted therapy, new drugs development and radiosensitivity prediction of NPC.