摘要
目的探究萝卜硫素(SFN)对高级别脑胶质瘤替莫唑胺(TMZ)抵抗的影响。方法培养人高级别脑胶质瘤细胞U251,构建U251 TMZ抵抗细胞系,用二甲基亚砜(DMSO)及10μmol·L^-1 SFN处理U251亲本细胞作为对照A组及实验A组,用DMSO及10μmol·L^-1 SFN处理U251 TMZ抵抗细胞作为对照B组及实验B组。用CCK-8实验检测各组细胞TMZ半抑制浓度(IC50),用实时荧光定量聚合酶链反应检测O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)和异柠檬酸脱氢酶1(IDH1)mRNA的表达水平。结果实验A组、实验B组、对照A组和对照B组的TMZ IC50值分别为(2.51±0.31),(4.43±1.26),(2.53±0.85)和(6.94±0.43)μg·mL^-1,MGMT mRNA相对表达水平分别为0.48±0.05,0.57±0.05,1.00±0.08和1.00±0.08,IDH1 mRNA相对表达水平分别为1.71±0.07,1.58±0.05,1.00±0.06和1.00±0.06。实验A组的MGMT和IDH1 mRNA相对表达水平与对照A组比较,差异均有统计学意义(均P<0.05);实验B组的上述指标与对照B组比较,差异均有统计学意义(均P<0.05)。结论SFN可通过下调高级别脑胶质瘤细胞中MGMT的表达,上调IDH1的表达,从而提高细胞对TMZ的敏感性。
Objective To investigate the effect of sulforaphane(SFN)on temozolomide(TMZ)resistance in high-grade brain gliomas.Methods Human glioma cells U251 were cultured and U251 TMZ resistant cells were constructed.U251 parental cells were treated with dimethylsulfoxide(DMSO)and 10μmol·L^-1 SFN as control A group and experimental A group,respectively.U251 TMZ resistant cells were treated with DMSO and 10μmol·L^-1 SFN as control group B and experimental B group,respectively.The 50%inhibitory concentration(IC50)of TMZ in each group was detected by CCK-8.The mRNA expression levels of O6-methylguanine-DNA methyltransferase(MGMT)and isocitrate dehydrogenase-1(IDH1)were detected by real-time fluorescence quantitative polymerase chain reaction.Results The IC50 values of TMZ in experimental A,experimental B,control A and control B groups were(2.51±0.31),(4.43±1.26),(2.53±0.85)and(6.94±0.43)μg·mL^-1,the relative expression levels of MGMT mRNA were 0.48±0.05,0.57±0.05,1.00±0.08 and 1.00±0.08,the relative expression levels of IDH1 mRNA were 1.71±0.07,1.58±0.05,1.00±0.06 and 1.00±0.06,respectively.The differences of MGMT and IDH1 mRNA were statistically significant between experimental A group and the control A group(all P<0.05).The differences of the above indexes were statistically significant between experimental B group and control B group(all P<0.05).Conclusion SFN can significantly down-regulate the expression of MGMT in high-grade glioma,and up-regulate the expression of IDH1,then promote the cell sensitivity of TMZ.
作者
李季芳
冯基高
黄海燕
胡建平
LI Ji-fang;FENG Ji-gao;HUANG Hai-yan;HU Jian-ping(Department of Nutrition,Hainan General Hospital,Haikou 570311,Hainan Province,China;Department of Neurosurgery,The Second Affiliated Hospital of Hainan Medical College,Haikou 570100,Hainan Province,China;Department of Medical Genetics and Prenatal Diagnosis,Hainan Women and Children’s Medical Center,Haikou 570206,Hainan Province,China;BY-HEALTH Co.,Ltd,Zhuhai 519090,Guangdong Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2020年第19期3053-3056,共4页
The Chinese Journal of Clinical Pharmacology
基金
海南省医药卫生科研课题资助项目(1801032099A2001)。
关键词
替莫唑胺
萝卜硫素
高级别脑胶质瘤
化疗抵抗
temozolomide
sulforaphane
high-grade glioma
chemotherapeutic resistance
