常山酮抑制肝癌HepG2细胞活性及机制初步研究  

Preliminary study on the mechanism of halofuginone inhibiting the activity of HepG2 cells

作　　者：陈孟旸 淮瑞平 杨丹妮 雷利杰 蒲秋霖 熊莉丽[2] CHEN Meng-yang;HUAI Rui-ping;YANG Dan-ni;LEI Li-jie;PU Qiu-lin;XIONG Li-li(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu 610000,China;School of Chemistry,Southwest Jiaotong University,Chengdu 610000,China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610000 [2]西南交通大学化学学院,四川成都610000

出　　处：《药学学报》2024年第2期368-373,共6页Acta Pharmaceutica Sinica

基　　金：中央高校基本科研业务费专项资金资助(2682020ZT112);四川省中医药管理局项目(2021XYCZ008);四川省科技厅重点研发计划项目(2022YFS0437)。

摘　　要：探讨常山酮(halofuginone)抑制肝细胞癌(hepatocellular carcinoma,HCC)细胞活性的作用及机制。以肝癌HepG2细胞为主要研究对象,使用CCK-8法、Transwell法、流式细胞术检测不同浓度和时间处理下,常山酮对HepG2细胞活性、细胞迁移、细胞周期和细胞凋亡的影响。通过实时荧光定量PCR(qPCR)和Western blot检测常山酮处理后细胞中柠檬酸合酶(citrate synthase,CS)、酮戊二酸脱氢酶(ketoglutarate dehydrogenase,OGDH)和异柠檬酸脱氧酶(isocitrate deoxygenase,IDH)的表达水平。与空白组相比,常山酮显著抑制HepG2细胞活性(P<0.01),降低HepG2细胞迁移率(P<0.01),诱导肝癌HepG2细胞凋亡(P<0.01),促使HepG2细胞周期停滞在S期(P<0.01)。常山酮处理后肝癌HepG2细胞中三羧酸循环关键酶CS、IDH3和OGDH表达量上调,异柠檬酸脱氢酶同工酶IDH1和IDH2表达量下调。常山酮可抑制肝癌HepG2细胞增殖和迁移,促进细胞凋亡并存在明显的剂量依赖性效应,这可能与促进细胞有氧代谢有关。This study aimed to investigate halofuginone's inhibitory effect and mechanism on the activity of hepatocellular carcinoma cells.HepG2 cells were used to detect the effects of halofuginone.After treatment,cell activity,cell migration,cell cycle,and cell apoptosis were detected by CCK-8,transwell,and flow cytometry,respectively.The expression levels of growth and metabolism-related factors such as citrate synthase(CS),ketoglutarate dehydrogenase(OGDH),and isocitrate deoxygenase(IDH)were detected by real-time quantitative PCR and Western blot.Compared with the control group,the activity of HepG2 cells was significantly inhibited by halofuginone(P<0.01),the migration rate of HepG2 cells was decreased(P<0.01),the apoptosis of HepG2 cells was induced(P<0.01),and the cell cycle was arrested in S phase(P<0.01).The expression levels of tricarboxylic acid key enzymes CS,IDH3,and OGDH were up-regulated,the expression level of isocitrate dehydrogenase isoenzymes IDH1 and IDH2 were down-regulation.In conclusion,halofuginone can inhibit the proliferation and migration of HepG2 cells and promote apoptosis in a dose-dependent manner,which may be due to the promotion of the aerobic metabolism of cells.

关 键 词：常山酮 三羧酸循环 HEPG2细胞 异柠檬酸脱氢酶 有氧代谢 

分 类 号：R966[医药卫生—药理学]