异甘草素通过介导拓扑异构酶Ⅰ对脑胶质瘤细胞生长抑制的研究  

Inhibition of glioma cell growth by isoliquiritigenin via regulating topoisomeraseⅠ

作　　者：钟敬波[1] 徐成[2] ZHONG Jing-bo;XU Cheng(Department of Pharmacy,Hainan General Hospital,Haikou 570311,Hainan Province,China;School of Life Sciences and Biopharmaceutics,Shenyang Pharmaceutical University,Shenyang 110000,Liaoning Province,China)

机构地区：[1]海南省人民医院药学部,海南海口570311 [2]沈阳药科大学生命科学与生物制药学院,辽宁沈阳110000

出　　处：《中国临床药理学杂志》2022年第18期2143-2146,共4页The Chinese Journal of Clinical Pharmacology

基　　金：海南省卫生计生行业科研基金资助项目(18A200092)。

摘　　要：目的探讨异甘草素对脑胶质瘤U87细胞生长的抑制作用。方法将脑胶质瘤U87细胞分为空白组、对照组和实验组。空白组给予0.5μmol·L^(-1)二甲基亚砜150μL;对照组给予0.5μmol·L^(-1)喜树碱150μL;实验组给予0.5μmol·L^(-1)异甘草素150μL。用噻唑蓝法检测细胞的生长抑制率,用蛋白质印迹法检测胱天蛋白酶-3(Caspase-3)蛋白的表达水平。分别用0.01~100.00μmol·L^(-1)的喜树碱和异甘草素处理脑胶质瘤U87细胞,并用琼脂糖凝胶电泳法测定其对拓扑异构酶Ⅰ(topoisomeraseⅠ,TOPⅠ)活性的影响。结果干预12,24,36和48 h后,与空白组比较,实验组和对照组的增殖均受到明显的抑制,且实验组的增殖抑制率均显著大于对照组,并随着时间延长更为显著。在高浓度(10.00~100.00μmol·L^(-1))范围内,异甘草对TOPⅠ抑制率均显著高于喜树碱,差异均有统计学意义(均P<0.05)。干预24,48和72 h后,实验组和对照组的Caspase-3蛋白相对表达水平(24.12±2.35,41.55±3.15,67.76±4.26和18.17±1.71,35.65±4.12,58.94±5.13)均较空白组(12.18±0.96,14.23±1.33,15.34±1.43)明显增加,差异均有统计学意义(均P<0.05);实验组的Caspase-3蛋白表达水平均显著高于对照组,差异均有统计学意义(均P<0.05)。结论异甘草素可通过介导拓扑异构酶TOP I活性,发挥抑制脑胶质瘤U87细胞增殖的作用。Objective To investigate the growth inhibitory effect of isoliquiritigenin on U87 glioma cells.Methods In vitro cultured U87 glioma cells were divided into blank,control and experimental groups.Blank group was treated with 0.5μmol·L^(-1)dimethyl sulfoxide 150μL.Control group was treated with 0.5μmol·L^(-1)camptothecin 150μL.Experimental group was treated with 0.5μmol·L^(-1)isoliquiritigenin 150μL.The growth inhibition rate of cells was measured by methyl thiazolyl tetrazolium.The expression levels of Caspase-3 protein were measured by Western blot.U87 glioma cells were treated with camptothecin and isoliquiritigenin covering a concentration range from 0.01 to 100.00μmol·L^(-1),respectively.Thereafter,the effect of isoliquiritigenin on the activity of topoisomeraseⅠ(TOPⅠ)was assessed using agarose gel electrophoresis.Results Compared with blank group,the cell proliferation was obviously inhibited in experimental and control groups after 12,24,36 and 48 h.Moreover,the proliferation inhibition rate in the experimental group was significantly greater than that in the control group,and was a time-dependent manner.In the high concentration range(10.00-100.00μmol·L^(-1)),isoliquiritigenin intervention had a greater inhibition on TOP I activity than that of camptothecin intervention,and the differences were statistically significant(all P<0.05).After 24,48 and 72 h of intervention,the Caspase-3 protein expression levels of experimental group were24.12±2.35,41.55±3.15,67.76±4.26 and the control group were 18.17±1.71,35.65±4.12,58.94±5.13,which were statistically higher than that of blank group(12.18±0.96,14.23±1.33,15.34±1.43);the differences were statistically significant(all P<0.05).The expression level of Caspase-3 protein in the experimental group was significantly higher than that in the control group,and all the differences were significant(all P<0.05).Conclusion Isoglycyrrhizin can inhibit the proliferation of U87 glioma cells by mediating the activity of TOPⅠ.

关 键 词：异甘草素 喜树碱 脑胶质瘤U87细胞 生长抑制 

分 类 号：R28[医药卫生—中药学]