Aurora-A促进鼻咽癌化疗抵抗的机制研究  

Mechanism of Aurora-A to promote chemoresistance in nasopharyngeal carcinoma

作　　者：范小琴 宋健 王雨洁 吴汉伟[2] 陆璐[3] 聂国辉[2,3] FAN Xiaoqin;SONG Jian;WANG Yujie;WU Hanwei;LU Lu;NIE Guohui(Department of Otolaryngology,the First Affiliated Hospital,Sun Yat-Sen University,Guangzhou,Guangdong, 510080,China;Institute of Translational Medicine,the Second People's Hospital of Shenzhen,Shenzhen,Guangdong,518035,China;Department of Otolaryngology,the Second People's Hospital of Shenzhen,Shenzhen,Guangdong,518035,China)

机构地区：[1]中山大学附属第一医院耳鼻咽喉科,广东广州510080 [2]深圳市第二人民医院转化医学研究院,广东深圳518035 [3]深圳市第二人民医院耳鼻咽喉科,广东深圳518035

出　　处：《中国耳鼻咽喉头颈外科》2019年第1期5-8,共4页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：中国博士后基金(2018M622876;2017M622877);深圳市科技创新委员会项目(JCYJ20170306091657539;JCYJ20170306091452714;JCYJ20170302165727389)联合资助

摘　　要：目的探讨丝/苏氨酸蛋白激酶Aurora-A促进鼻咽癌化疗抵抗的机制。方法应用Western blot和Q-PCR检测鼻咽癌组织及癌旁正常组织中Aurora-A的表达水平。选取Aurora-A高表达的鼻咽癌细胞系CNE2,添加Aurora-A激酶抑制剂60nmVX680处理8小时后,加入浓度为10μg/ml的顺铂处理24小时,收集细胞通过流式细胞术检测细胞凋亡情况,同时WB和Q-PCR检测细胞凋亡相关信号通路蛋白的表达情况。结果 Aurora-A在鼻咽癌组织中表达水平明显高于癌旁正常组织,相对于正常鼻咽细胞NP69,Aurora-A在不同鼻咽癌细胞中表达显著升高且在CNE2中表达最高;相对于未处理CNE2,添加顺铂或/和Aurora-A抑制剂VX680处理的CNE2细胞能显著促进鼻咽癌细胞凋亡及p-AKT、p21及Cleaved-Caspase-3的表达。结论 Aurora-A通过p-AKT/p21/Cleaved-Caspase-3通路促进鼻咽癌的化疗抵抗。OBJECTIVE To explore the mechanism of Aurora kinase A (Aurora-A)promoting cancer cell chemotherapy resistance in nasopharyngeal carcinoma.METHODS The expression of Aurora-A in nasopharyngeal carcinoma tissues and adjacent tissues were detected by Western bolt and Q-PCR.The high-expressing Aurora A cell line CNE2 was used to detected the cell apoptosis and the expression of key pathway marker protein after Aurora-A inhibitor VX680 and cisplatin treatment by using Flow cytometry and WB.RESULTS The expression of Aurora-A in nasopharyngeal carcinoma tissues was significantly higher than that in adjacent tissues. Comparing to normal nasopharyngeal cells NP69,Aurora-A was significantly highly expressed in all of nasopharyngeal carcinoma cells and was highest in CNE2.Inhibiton of Aurora-A increased the cell apoptosis and the expression .of p-AKT,p21 and Cleaved-Caspase-3 after using cisplatin or the Aurora-A inhibitor VX680 treatment.CONCLUSION The results shown that Aurora-A confer chemoresistance to cisplatin treatment through p-AKT/p21/Cleaved-Caspase-3 pathway.

关 键 词：鼻咽肿瘤 细胞凋亡 顺铂 化疗抵抗 丝/苏氨酸蛋白激酶 

分 类 号：R739.63[医药卫生—肿瘤]