嵌合分子靶向降解鼻咽癌细胞表皮生长因子受体的实验研究  

Targeted degradation of epidermal growth factor receptor in nasopharyngeal carcinoma by chimeric molecule

作　　者：董洁[1] 李双[1] 王庆[1] 肖伟[1] 尹述成[1] 

机构地区：[1]武汉大学中南医院耳鼻咽喉头颈外科,武汉430000

出　　处：《临床耳鼻咽喉头颈外科杂志》2017年第4期297-300,共4页Journal of Clinical Otorhinolaryngology Head And Neck Surgery

基　　金：国家自然科学基金资助(No:81372881)

摘　　要：目的:检测合成的蛋白靶向嵌合分子(EGF-PROTAC)通过泛素-蛋白酶体途径体外对人鼻咽癌CNE-2细胞表皮生长因子受体(EGFR)靶向降解作用,并证实对该细胞增殖、凋亡的影响。方法:EGF-PROTAC处理细胞后,应用Western blot技术分析EGFR蛋白表达水平;CKK-8、流式细胞术、Transwell侵袭实验检测EGF-PROTAC对CNE-2产生的生物学效应。结果:Western blot技术显示EGF-PROTAC组EGFR蛋白的表达水平显著低于对照组(P<0.05);CKK-8法显示EGF-PROTAC组3、6、9、12hCNE-2细胞存活率显著低于溶剂对照组(P<0.05);流式细胞术显示EGF-PROTAC组细胞凋亡指数显著高于对照组(P<0.05);Transwell法显示EGF-PROTAC组CNE-2细胞侵袭到Transwell小室滤膜下细胞数显著低于溶剂对照组(P<0.05)。结论:EGF-PROTAC能够靶向降解CNE-2细胞的EGFR,在体外能抑制鼻咽癌细胞的生长、促进凋亡。Objective：The aim of this study was to investigate targeted degradation of the epidermal growth factor receptor（EGFR）by chimeric molecules（EGF-PROTAC）via the ubiquitin-proteasome pathway on human nasopharyngeal carcinoma CNE-2cells and demonstrate the regulative effect on the proliferation and apoptosis of the CNE-2cells.Method：After the EGF-PROTAC treating CNE-2cells in vitro,the biological effects of the EGFPROTAC was detected by western blot,CKK-8assay,flow cytometry and Transwell migration assay in CNE-2cells.Result：The expression level of EGFR proteins in the EGF-PROTAC-treated group was lower than the control group（P〈0.05）;CKK-8assay results showed that CNE-2cells survival rate at 3,6,9and 12 hdecreased greatly than the control group（P〈0.05）;Flow cytometry indicated that the apoptosis index of the CNE-2cells in EGF-PROTAC-treated group was significantly higher than the control group（P〈0.05）;The invasion ability detected that the number of CNE-2cells in the EGF-PROTAC-treated group was significantly lower than the control group（P〈0.05）.Conclusion：The chimeric molecule（EGF-PROTAC）can target the degradation of epidermal growth factor receptors（EGFR）and effectively inhibit the growth of the CNE-2cells and promote apoptosis in vitro.

关 键 词：鼻咽肿瘤 嵌合分子 泛素化 表皮生长因子受体 

分 类 号：R739.63[医药卫生—肿瘤]