黄连素调节非小细胞肺癌细胞糖酵解水平并抑制A549细胞EMT的发生  

Berberine regulating the level of glycolysis in non-small cell lung cancer cells and inhibiting the occurrence of EMT in A549 cells

作　　者：吴国成[1] 陈焕[1] WU Guo-cheng;CHEN Huan(Department of Respiratory and Critical Care,Navy Anqing Hospital,Anqing,Anhui 246003,China)

机构地区：[1]海军安庆医院呼吸与危重症医学科,安徽安庆246003

出　　处：《临床肺科杂志》2020年第8期1206-1211,共6页Journal of Clinical Pulmonary Medicine

摘　　要：目的本研究旨在探讨黄连素(berberine,BBR)在抑制肺癌侵袭转移中的应用价值并探索相关机制。方法 CCK8细胞活性检测法检测不同浓度的BBR对A549细胞增殖活性的影响;迁移和侵袭实验检测BBR对A549细胞侵袭和迁移能力的影响;Western blot检测BBR对A549细胞间质转化(epithelial-mesenchymal transition, EMT)相关蛋白表达的影响;代谢通量测定检查BBR对A549细胞糖酵解水平的调节作用;PCR检测BBR对糖酵解相关酶HK1、HK2、LDHA基因表达的影响;使用重组HK2,研究激活糖酵解进程对BBR抑制EMT进程的影响。结果低剂量BBR(<8μm/L)轻微上调细胞增殖活性,高浓度BBR(64 um/L)下调细胞增殖活性;高剂量BBR能够抑制A549细胞发生EMT,减弱癌细胞的侵袭和迁移能力;BBR通过下调HK2表达,抑制A549糖酵解水平;BBR抑制A549细胞侵袭和迁移能力是通过调节糖酵解水平实现的。结论高浓度BBR下调A549细胞内HK2的表达进而调节肺癌细胞糖酵解;BBR抑制A549细胞侵袭和迁移能力可能与抑制糖酵解活性有关。Objective To investigate the value of berberine(BBR) in inhibiting invasion and metastasis of lung cancer and to explore related mechanisms. Methods We analyzed the effect of different concentrations of BBR on the proliferation activity of A549 cells by CCK8 cell activity assay. The migration and invasion assay were conducted to explore the aggressiveness of lung cancer. The expression of N-cadherin,E-cadherin,Vimentin,Fibronectin,β-catenin,HK2 and GLUT1 were detected by western blot and immunofluorescence. ECAR was measured using a Seahorse XF96 extracellular flux analyzer. Results The limited dose of BBR had the function of inhibiting the proliferation activity of A549 cells. BBR could inhibit EMT in A549 cells and decrease cell invasion and migration. The ability of BBR to inhibit the invasion and migration of A549 cells was achieved by regulating the level of glycolysis. Conclusion High concentration of BBR can down-regulate the expression of HK2 in A549 cells and regulate the glycolysis of lung cancer cells. BBR inhibited the invasion and migration of A549 cells may be related to the inhibition of glycolysis activity.

关 键 词：黄连素 肺癌 转移 代谢 EMT 

分 类 号：R285.5[医药卫生—中药学]