连翘环己醇通过JAK2-STAT3信号通路对肝癌细胞凋亡的影响  

Effects of forsythinol on apoptosis of hepatocellular carcinoma cells through the JAK2-STAT3 signaling pathway

作　　者：张欣[1] 黄冬祥[2] 汤灿辉[1] 黄志飘 ZHANG Xin;HUANG Dong-xiang;TANC Can-hui;HUANG Zhi-piao(Department of Pharmacy,Jiangxi College of Traditional Chinese Medicine,Fuzhou 344100,Jiangxi Province,China;Department of Infectious Diseases,Fuzhou First People's Hospital,Fuzhou 344100,Jiangxi Province,China)

机构地区：[1]江西中医药高等专科学校药学系,江西抚州344100 [2]抚州市第一人民医院感染科,江西抚州344000

出　　处：《中国临床药理学杂志》2024年第19期2837-2841,共5页The Chinese Journal of Clinical Pharmacology

基　　金：江西省中医药科技计划一般基金资助项目(2023B1306);江西省教育厅科技计划一般基金资助项目(GJJ2205915)。

摘　　要：目的探讨连翘环己醇(Fo)通过Janus激酶2/信号转导与转录激活子3(JAK2/STAT3)信号通路调控基质金属蛋白酶-2(MMP2)表达对肝癌细胞的影响。方法将SMMC-7721细胞分为低、中、高剂量实验组和对照组抑制药组、激活药组。对照组加入等体积二甲基亚砜(DMSO);低、中、高剂量实验组分别用50、200、500μg·mL^(-1)Fo处理;抑制药组在中剂量实验组的基础上,加入50μmol·L^(-1)JAK2/STAT3抑制药AG490;激活药组在中剂量实验组的基础上,加入10μmol·L^(-1)JAK2/STAT3激活药Broussonin E。用脱氧核苷酸末端转移酶介导的dUTP缺口末端标记(TUNEL)法检测细胞凋亡水平,用蛋白质印迹法检测蛋白的表达水平,用实时定量聚合酶链反应(qRT-PCR)检测mRNA的表达水平。结果对照组、中剂量实验组、抑制药组和激活药组的凋亡率分别为(19.94±4.88)%、(27.04±5.27)%、(15.36±3.40)%和(46.66±7.89)%,磷酸化JAK2蛋白相对表达水平分别为1.00±0.13、0.73±0.11、1.33±0.17和0.26±0.07,磷酸化STAT3蛋白相对表达水平分别为1.00±0.12、0.27±0.04、0.88±0.13和0.12±0.04,MMP2 mRNA相对表达水平分别为1.00±0.14、0.68±0.08、1.17±0.17和0.51±0.09。中剂量实验组的上述指标与对照组、抑制药组的上述指标和激活药组比较,在统计学上差异均有统计学意义(P<0.05,P<0.001)。结论Fo促进肝癌细胞的凋亡,其机制或与Fo调控JAK2-STAT3信号通路对MMP2表达的影响有关。Objective To investigate the effects of forsythinol(Fo)on the expression of matrix metalloproteinase-2(MMP2)in hepatoma cells through Janus kinase 2/signal transduction and transcriptional activator 3(JAK2/STAT3)signaling pathway.Methods SMMC-7721 cells were divided into experimental-L,-M,-H groups,control group,inhibitor group and activator group.The control group was added with equal volume dimethyl sulfoxide(DMSO);the experimental-L,-M,-H groups were treated with 50,200,500μg·mL^(-1)Fo;and the inhibitor group was added with 50μmol·L^(-1)JAK2/STAT3 inhibitor AG490based on the experimental-M group.In the activator group,10μmol·L^(-1)JAK2/STAT3 activator Broussonin E was added to the experimental-M group.Apoptosis was detected by deoxynucleotide terminal transferasemediated dUTP notch end labeling(TUNEL);protein expression was detected by Western blot;real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect mRNA levels.Results The apoptosis rates of control group,experimental-M group,inhibitor group and activator group were(19.94±4.88)%,(27.04±5.27)%,(15.36±3.40)%and(46.66±7.89)%,respectively;the relative expression levels of phosphorylated JAK2 protein were 1.00±0.13,0.73±0.11,1.33±0.17 and 0.26±0.07,respectively;the relative expression levels of phosphorylated STAT3 protein were 1.00±0.12,0.27±0.04,0.88±0.13 and 0.12±0.04,respectively;the mRNA relative expression levels of MMP2 were 1.00±0.14,0.68±0.08,1.17±0.17 and 0.51±0.09,respectively.Compared with experimental-M group and control group,inhibitor group and activator group,there were statistically significant differences(P<0.05,P<0.001).Conclusion Fo promotes apoptosis of hepatocellular carcinoma cells,and its mechanism may be related to the effect of Fo on the expression of MMP2 by regulating JAK2-STAT3 signaling pathway.

关 键 词：连翘环己醇 肝癌 Janus激酶2-信号转导和转录激活子3 基质金属蛋白酶2 基质金属蛋白酶9 

分 类 号：R28[医药卫生—中药学]