2-脱氧-D-葡萄糖通过PI3K/AKT通路调控线粒体自噬抑制非小细胞肺癌的机制研究OA

Objective:To investigate the effect of 2-deoxy-D-glucose(2-DG)on non-small cell lung cancer(NSCLC)A549 cells and mitochondrial function by regulating mitophagy through the phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT)signaling pathway.Methods:NSCLC A549 cells were selected and randomly divided into 5 groups:The control group,2-DG low dose group(5 mmol/L),2-DG middle dose group(10 mmol/L),2-DG high dose group(20 mmol/L)and LY294002 group(20 μmol/L)were treated with blank control,2-DG low dose group(5 mmol/L),2-DG middle dose group(10 mmol/L)and LY294002 group(20 μmol/L).Cell viability was de-tected by CCK-8 assay.Flow cytometry was used to detect the apoptosis rate and mitochondrial reactive oxygen spe-cies(ROS)level.Mitochondrial membrane potential was measured by laser confocal microscopy.Western blot was used to detect the expression of PI3K/AKT pathway and autophagy-related proteins.Results:Compared with the blank control group,cell viability and invasion ability were decreased,and the apoptosis rate was increased in the 2-DG dose groups and the LY294002 group in a dose-dependent manner(all P＜0.05).The above indicators in the 2-DG high-dose group were similar to those in the LY294002 group(P＞0.05).Compared with the blank control group,the relative fluorescence intensity of mitochondrial membrane potential was decreased,and the relative fluores-cence intensity of mitochondrial reactive oxygen species(ROS)was increased in the 2-DG low-,medium-,and high-dose groups as well as the LY294002 group,all in a dose-dependent manner(all P＜0.05).The mitochondrial mem-brane potential and ROS levels in the 2-DG high-dose group were similar to those in the LY294002 group(all P＞0.05).Compared with the blank control group,the relative expression levels of p-PI3K,p-AKT,and p62 proteins were decreased,while the expression levels of LC3 Ⅱ and LC3 Ⅰ proteins were increased in the 2-DG low-,medium-,and high-dose groups and the LY294002 group,all in a dose-dependent manner(all P＜0.05).The changes in the ex-pression of the above proteins in the 2-DG high-dose group were similar to those in the LY294002 group(all P＞0.05).Conclusion:2-DG can activate mitophagy by inhibiting the PI3K/AKT signaling pathway,thereby reducing A549 cell viability and inducing apoptosis.