AKT抑制剂E20诱导鼻咽癌细胞凋亡和自噬  

A new AKT inhibitor induces apoptosisand autophagyin nasopharyngeal carcinoma cells

作　　者：张杰[1] 杨煜锋 胡婷婷 吴聪 杨子飞 吴贤敏[1] ZHANG Jie;YANG Yufeng;HU Tingting;WU Cong;YANG Zifei;WU Xianmin(Department of Otolaryngology-Head and Neck Surgery,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China;Department of Gastroenterology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第一医院耳鼻咽喉-头颈外科,浙江温州325015 [2]温州医科大学附属第一医院消化内科,浙江温州325015

出　　处：《温州医科大学学报》2023年第1期22-28,共7页Journal of Wenzhou Medical University

基　　金：温州市基础性科研项目(Y2020027)。

摘　　要：目的:通过细胞实验探讨一种新的AKT抑制剂E20对人类CNE-2细胞的抗肿瘤效应及其内在的调节机制。方法:CCK8法检测E20处理后CNE-2细胞的活性;流式细胞术检测细胞凋亡;Mito-SOX流式数据分析检测线粒体ROS水平的变化;Western blot检测E20处理后细胞凋亡相关蛋白(AIF和Bcl-2)和自噬相关蛋白(LC3B-I、LC3B-II和P62)表达的变化;透射电子显微镜观察细胞线粒体超微结构和自噬小体的变化。结果:E20显著抑制CNE-2细胞增殖,促进其凋亡,且呈时间剂量依赖性(P<0.05);E20处理后CNE-2细胞线粒体ROS水平显著升高,细胞凋亡蛋白AIF显著升高,抗凋亡蛋白Bcl-2显著降低,自噬相关蛋白LC3B-II显著升高、P62显著降低(均P<0.05);透射电镜发现E20处理后的细胞线粒体受损,自噬小体增多。结论:E20可以通过线粒体途径诱导细胞凋亡,同时可能激活其自噬来抑制鼻咽癌细胞的增殖,为鼻咽癌的治疗提供了一种潜在的化疗策略。Objective:To investigate the antitumor effect of E20,a novel AKT inhibitor,on human CNE-2cells and the underlying regulatory mechanism.Methods:CCK8 assay was used to detect the activity of CNE-2cells after E20 treatment.Cell apoptosis was detected by flow cytometry.Mito-sox were analyzed to detect the changes of mitochondrial ROS levels.Western blot was used to detect the expression of apoptosis-related proteins(AIF and Bcl-2)and autophagy-related proteins(LC3B-I,LC3B-II and P62)after E20 treatment.Transmission electron microscopy was used to observe the ultrastructure of mitochondria and the change of the autophagosomes.Results:E20 significantly inhibited the proliferation and promoted apoptosis of CNE-2 cells in a time-dosedependent manner(P<0.05).After E20 treatment,the mitochondrial ROS level of CNE-2 cells was significantly increased,apoptosis protein AIF was significantly increased,and anti-apoptotic protein Bcl-2 was significantly decrease(all P<0.05).Autophagy-related protein LC3B-II was significantly increased,and P62 was significantly decreased(P<0.05).Transmission electron microscopy(TEM)showed that mitochondria were damaged and autophagosomes increased in E20 treated cells.Conclusion:E20 can inhibit the proliferation of NPC cells by inducing apoptosis through mitochondrial pathway and possibly activating autophagy,which provides a potential chemotherapy strategy for the treatment of NPC.

关 键 词：AKT抑制剂 活性氧 自噬 凋亡 鼻咽癌 

分 类 号：R285.5[医药卫生—中药学]