甘草酸通过激活TRPV4诱导线粒体自噬抑制脑胶质瘤细胞的生长  

Glycyrrhizic acid inhibits the growth of glioma cells by activating TRPV4-induced mitophagy

作　　者：陈思[1] 陆斌[1] 毕堃 尹文伟 CHEN Si;LU Bin;BI Kun;YIN Wenwei(Tangshan Workers'Hospital,Hebei Tangshan 063000,China)

机构地区：[1]唐山市工人医院,河北唐山063000

出　　处：《现代肿瘤医学》2023年第15期2776-2781,共6页Journal of Modern Oncology

基　　金：河北省卫生健康委员会项目(编号:20200312)。

摘　　要：目的:探讨甘草酸(glycyrrhizic acid,GA)在脑胶质瘤中的作用及机制研究。方法:采用细胞克隆形成实验和CCK-8方法检测GA、TRPV4抑制剂HC-067047对胶质瘤细胞活力的影响;采用Western blot法检测线粒体自噬相关蛋白PINK1、Parkin和LC3蛋白的表达水平;采用电镜检测线粒体自噬情况;构建人脑胶质瘤小鼠原位模型,使用小动物活体生物发光成像系统监测肿瘤生长情况并分析各组小鼠的生存期,并监测小鼠体重。结果:CCK-8实验结果表明GA显著抑制胶质瘤细胞增殖活力,TRPV4抑制剂HC-067047对细胞增殖活力有促进作用,并且TRPV4抑制剂HC-067047可以逆转GA的抑制作用;Western blot实验结果表明GA可诱导胶质瘤细胞线粒体自噬,促进自噬相关蛋白PINK1、Parkin和LC3蛋白的表达;电镜检测发现GA可以促进胶质瘤细胞中的线粒体自噬,TRPV4抑制剂HC-067047可以逆转GA的促自噬作用;小动物活体生物发光成像结果显示,GA可明显抑制脑胶质瘤的生长,显著延长脑胶质瘤小鼠的生存期。结论:GA可通过激活TRPV4诱导线粒体自噬,进而抑制脑胶质瘤细胞的生长。Objective:To investigate the role and mechanism of glycyrrhizic acid(GA)in glioma.Methods:The effects of GA and TRPV4 inhibitor HC-067047 on glioma cell viability were examined by cell clone formation assay and CCK-8 experiments.The expression levels of mitochondrial autophagy-related proteins PINK1,Parkin and LC3 were examined by Western blot.The mitochondrial autophagy was examined by electron microscopy.Human glioma mouse in situ model was constructed.The tumor growth was monitored using a small animal in vivo bioluminescence imaging system and the survival of each group of mice was analyzed,and the body weight of mice was monitored.Results:CCK-8 assay showed that GA significantly inhibited the viability of glioma cells,and the TRPV4 inhibitor HC-067047 promoted the cell proliferation viability,and the TRPV4 inhibitor HC-067047 could reverse the inhibitory effect of GA.Western blot showed that GA could induce mitochondrial autophagy in glioma cells and promote the expression of autophagy-related proteins PINK1,Parkin and LC3 proteins.Electron microscopic detection revealed that GA could promote mitochondrial autophagy in glioma cells and the TRPV4 inhibitor HC-067047 could reverse the pro-autophagic effect of GA.The results of bioluminescence imaging in small animals showed that GA could significantly inhibit the growth of glioma and significantly prolong the survival period of glioma mice.Conclusion:GA can induce mitochondrial autophagy through activation of TRPV4,which in turn inhibits the growth of glioma.

关 键 词：甘草酸 TRPV4 线粒体自噬 神经脑胶质瘤 

分 类 号：R730.264[医药卫生—肿瘤]