核仁素（NCL）蛋白在鼻咽癌等多种恶性肿瘤中高表达，并与肿瘤发生发展密切相关。NCL具有抑制细胞凋亡的功能，细胞凋亡与自噬密切相关，二者在肿瘤发生和治疗中都具有重要的意义。我们前期研究发现莪术醇能够抑制NCL的表达，诱导鼻咽癌细胞凋亡，并提高自噬标记物LC3II的表达。这些结果提示：莪术醇可能通过NCL调控鼻咽癌细胞自噬和凋亡发生。本项目拟在确定莪术醇诱导细胞自噬发生的基础上，结合其诱导细胞凋亡的活性，阐明自噬与凋亡的关系。构建过表达和沉默NCL细胞模型，确定NCL是否通过下游PI3K/Akt信号通路介导了莪术醇诱导的鼻咽癌细胞自噬及凋亡过程；并利用裸鼠体内成瘤实验验证NCL在莪术醇诱导细胞自噬与凋亡中的调控功能和机制。在此基础上，利用鼻咽癌临床标本，确证NCL，PI3K/Akt表达水平与临床病理特征的关系。此项目实施，将为莪术醇治疗鼻咽癌提供新的思路和科学依据。

Nucleolin (NCL) protein is highly expressed in a variety of malignant tumors, including nasopharyngeal carcinoma, and is closely related to the development of tumor. NCL can inhibit cell apoptosis who is closely related to autophagy, both apoptosis and autophagy play important role in the occurrence and treatment of cancers. Our previous studies have shown that curcumol can inhibit the expression of NCL, induce apoptosis of nasopharyngeal carcinoma cells, and enhance the expression of autophagy marker LC3II. These results suggest that NCL may regulate autophagy and apoptosis in nasopharyngeal carcinoma cells. The first aim of this project is to confirm the autophagy activity induced by curcumol and reveal the relationship between autophagy and apoptosis. Second, through NCL over-expression and silencing cell models of nasopharyngeal carcinoma cells, we determine whether the autophagy and apoptosis induced by curcumol is modulated by NCL mediated-PI3K/Akt signaling pathway, and use nude mice transplanted tumor models to verify the regulation function of NCL as in the cell models. Furthermore, the relationship between NCL，PI3K/Akt and clinical pathological features was confirmed by the clinical specimens of nasopharyngeal carcinoma. The completion of this project will provide new ideas and scientific basis for curcmol’s treatment of anti-nasopharyngeal carcinoma.