EphA2介导的细胞自噬在鼻咽癌紫杉醇耐药中的作用及分子机制研究

项目名称： EphA2介导的细胞自噬在鼻咽癌紫杉醇耐药中的作用及分子机制研究

项目编号： No.81202128

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 刘勇

作者单位： 中南大学

项目金额： 24万元

中文摘要： 自噬作用为目前肿瘤化疗耐药研究中的热点。前期研究表明：EphA2过表达后，①鼻咽部低分化鳞癌细胞5-8F对化疗药物紫杉醇的敏感性显著降低；②能引起自噬小体增加和自噬相关标记物LC3-Ⅱ蛋白表达升高，提示EphA2过表达能在鼻咽癌细胞中诱导出自噬现象。结合目前研究表明自噬作用与化疗耐药关系密切，我们设想EphA2可能通过介导自噬作用调控鼻咽癌细胞对紫杉醇的敏感性。为此我们利用慢病毒介导的EphA2过表达和沉默载体，在体内外实验中，改变鼻咽癌细胞EphA2的表达，观察改变后自噬及其通路蛋白的改变和对紫杉醇敏感性的影响；再通过阻断或诱导自噬作用，观察EphA2 改变所致的紫杉醇敏感性改变能否逆转。从而阐明EphA2 介导的自噬作用在鼻咽癌细胞紫杉醇化疗敏感性中的重要作用，为肿瘤紫杉醇耐药研究提供新的理论依据和实验基础。

中文关键词： 鼻咽癌；紫杉醇；自噬；化疗耐药；

英文摘要： Autophagy has been a hot spot in drug resistance of cancer chemotherapy. Our previous study has clearly demonstrated that EphA2 upregulation, on the one hand, led to drug resistance of Paclitaxel in human poor differentiated nasopharyngeal carinoma cell line 5-8F. On the other hand, EphA2 overexpression induced the increased formation of autophagosome and upregulation of autophagy-associated biomarker protein LC3-Ⅱ, indicating the potential associatin between EphA2 and autophagy phenomenon. Therefore, combined with the close association between autophagy and drug resistance of chemotherapy, we hypothesize that EphA2 may lead to drug resistance of chemotherapy in nasopharyngeal carcinoma (NPC) via modulating the process of autophagy. In order to test the hypothesis, we shall utilize lentivirus-mediated EphA2 overexpression and silencing vector to change EphA2 expression level in NPC cell lines. Autophagy process and its down signalling pathway and the drug sensitivity of NPC to paclitaxel are observed. Morever, autophagy process is impeded or enhanced to observe whether the changed response to paclitaxel and cisplatin mediated by EphA2 will be reversed. In summary, we clarify that EphA2 lead to drug resistance of chemotherapy in NPC via regulating autophagy process, which will provide novel theory and experiment

英文关键词： nasopharyngeal carcinoma；paclitaxel；autophagy；chemoresistance；