AKT抑制剂E20诱导鼻咽癌细胞凋亡和自噬

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。

A new AKT inhibitor induces apoptosisand autophagyin nasopharyngeal carcinoma cells

Objective: To investigate the antitumor effect of E20, a novel AKT inhibitor, on human CNE-2 cells and the underlying regulatory mechanism. Methods: CCK8 assay was used to detect the activity of CNE-2 cells 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-dose-dependent 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.