Annexin A1是一个候选抑瘤基因，与肿瘤细胞增殖、分化和凋亡密切相关。申请者前期研究发现：Annexin A1在放疗抵抗鼻咽癌组织和细胞中均表达下调/缺失，是p53参与鼻咽癌放射应答的蛋白质之一，可能与鼻咽癌放疗抵抗有关。本项目拟建立Annexin A1稳定上调的CNE2-IR细胞系，Annexin A1稳定下调的CNE2细胞系，通过体内和体外实验研究Annexin A1在鼻咽癌放疗抵抗中的作用。以建立的细胞系为样本，研究Annexin A1与p53的放射生物学活性及鼻咽癌放疗抵抗的关系；采用串联亲和纯化耦联质谱技术，鉴定Annexin A1的相互作用蛋白，构建Annexin A1在鼻咽癌放疗抵抗中的蛋白质调控网络，明确Annexin A1调控的关键靶蛋白及信号通路，阐明Annexin A1在鼻咽癌放疗抵抗中的作用机制，为鼻咽癌的放疗敏感性预测、靶向治疗和个体化放疗提供科学依据。

Annexin A1 is a potential tumor suppressor gene, is closely related to tumor cell proliferation, differentiation and apoptosis. In our previous study, we found that Annexin A1 was down-regulated or deletion in the nasopharyngeal carcinoma(NPC) tissue and cell line with radioresistance, and was one of the proteins that were involved in p53-mediated radioresponse in NPC. And it might be related to radioresistance of NPC. In this study, firstly, we will increase the expression of Annexin A1 in CNE2-IR cell line using gene transfection and knock down the expression of Annexin A1 in CNE2 cell line using siRNA techlique, analyze the radiosensitivity of these cell lines in vitro and in vivo, then evaluate its effect of the biological activity of p53 and its correlation with NPC radioresistance. Secondly, we will identify the proteins interacting with Annexin A1 using tandem affinity purification and 2D-LC-MS/MS technology, build the protein regulatory networks of Annexin A1 in NPC radioresistance, screen the important targetprotein regulated by Annexin A1, and find the key signaling pathway related to NPC radioresistance by bioinformatics analysis. This project helps not only to reveal the role and mechanism of Annexin A1 downregulation / deletion in the radioresistance for NPC, but also to provide a scientific basis for radiation sensitivity prediction, targeted therapy and individualized radiotherapy of NPC.