苯扎贝特通过AKT/mTOR通路抑制肺腺癌糖酵解机制研究  

Study on the mechanism of bezafibrate inhibiting glycolysis in lung adenocarcinoma through AKT/mTOR pathway

作　　者：李智斌 叶锦霞 巫艳 王桂平 LI Zhibin;YE Jinxia;WU Yan;WANG Guiping(Guangzhou Health Science College,Guangzhou 510450,China)

机构地区：[1]广州卫生职业技术学院,广东广州510450

出　　处：《广东药科大学学报》2024年第1期101-104,共4页Journal of Guangdong Pharmaceutical University

基　　金：广州市教育局青年人才科研项目(202032865)。

摘　　要：目的 通过观察苯扎贝特对肺腺癌A549细胞生长的抑制作用,探寻其可能的作用机制。方法 取对数生长期A549细胞,设苯扎贝特组(25、50、100、200、400μmol/L)、阴性对照组、空白对照组,药物干预48 h及72 h后,CCK-8法检测A549细胞增殖抑制率;测定细胞经药物作用后的葡萄糖及乳酸含量,计算葡萄糖消耗率及乳酸产量,评价不同浓度苯扎贝特对A549细胞有氧糖酵解的影响;免疫印迹法(Western blot)检测高中低浓度苯扎贝特组细胞中Akt、mTOR和PKM2的蛋白表达。结果 苯扎贝特能显著抑制肺腺癌A549细胞增殖,抑制作用与用药浓度成正比;苯扎贝特可影响A549细胞糖酵解过程,随着用药浓度增大,细胞中葡萄糖消耗量及乳酸产量不断减少;苯扎贝特可明显抑制Akt、mTOR和PKM2的蛋白表达,抑制作用呈现浓度依赖性。结论 苯扎贝特能够促进肺腺癌A549细胞凋亡,作用机制可能与抑制糖酵解途径,逆转肿瘤细胞的瓦博格效应有关。Objective To study the inhibitory effect and mechanism of bezafibrate on the growth of lung adenocarcinoma A549 cells.Methods Logarithmic growth stage A549 cells were selected and divided into bezafibrate groups(25,50,100,200,400µmol/L),negative control group,and blank control group.After 48 and 72 hours of drug intervention,the inhibition rate of A549 cell proliferation was detected by CCK-8 method.The contents of glucose and lactic acid in cell medium of each group were determined,the glucose consumption rate and lactic acid production were calculated,and the effects of different concentrations of bezafibrate on aerobic glycolysis of A549 cells were evaluated.The expression of Akt,mTOR and PKM2 protein in high,medium and low concentrations of bezafibrate groups were detected by western blot.Results Bezafibrate significantly inhibited the proliferation of lung adenocarcinoma A549 cells,and the inhibitory effect was proportional to the drug concentration.Bezafibrate affected the glycolysis process of A549 cells.With the increase of drug concentration,glucose consumption and lactic acid production in cells decreased.Bezafibrate inhibited the expression of Ak,mTOR and PKM2 protein in a concentration-dependent manner.Conclusion Bezafibrate can promote apoptosis of lung adenocarcinoma A549 cells,which may be related to inhibition of glycolysis pathway and reversal of warburg effect in tumor cells.

关 键 词：苯扎贝特 肺腺癌A549细胞 糖酵解 瓦博格效应 

分 类 号：R765[医药卫生—耳鼻咽喉科]