A new AKT inhibitor induces apoptosisand autophagyin nasopharyngeal carcinoma cells
ZHANG Jie1, YANG Yufeng1, HU Tingting2, WU Cong1, YANG Zifei1, WU Xianmin1
1.Department of Otolaryngology-Head and Neck Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China; 2.Department of Gastroenterology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China
ZHANG Jie,YANG Yufeng,HU Tingting, et al. A new AKT inhibitor induces apoptosisand autophagyin nasopharyngeal carcinoma cells[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(1): 22-28.
Abstract：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.
