广西医科大学学报2023,Vol.40Issue(12):1964-1971,8.DOI:10.16190/j.cnki.45-1211/r.2023.12.005
基于生物信息学及体外实验研究大黄素治疗胰腺癌的靶点
The target of emodin in the treatment of pancreatic cancer based on bioinformatics combined with in vitro experiments
摘要
Abstract
Objective:To study the target of emodin in the treatment of pancreatic cancer by bioinformatics and cell experiments.Methods:The pancreatic cancer transcriptome datasets GSE62452 and GSE28753 were ob-tained from the Gene Expression Omnibus(GEO)database,and the Traditional Chinese Medicine Systems Phar-macology Database and Analysis Platform(TCMSP)and PharmMapper Server were used to obtain the target of emodin.The target genes of the two were cross-screened to obtain the potential target genes of emodin in pancre-atic cancer.The DAVID database was used for KEGG and GO functional enrichment analysis of target genes,and GEPIA database was used for differential expression and survival analysis of potential target genes.Pancreatic cancer cells were culturedin vitroand cell counting kit-8(CCK-8)assay was used to detect the effect of different concentrations of emodin on the proliferation of pancreatic cancer cells.The cells were divided into normal con-trol group and different concentrations of emodin group.The real-time fluorescence quantitative PCR(RT-qPCR)was used to detect the mRNA expression of plasminogen activator urokinase(PLAU),tyrosine kinase receptor(MET),epoxide hydrolase 2(EPHX2),and matrix metalloproteinase 1(MMP1).Western blotting was used to de-tect the expression of EPHX2 protein.Results:Seventeen common target genes of emodin and pancreatic cancer were obtained.Functional enrichment analysis showed that the target genes were mainly enriched in extracellular space,extracellular vesicle,serine endopeptidase activity,protein hydrolysis,calcium ion binding and other path-ways.Differential expression analysis showed that there were significant differences in MMP1,EPHX2,PLAU,MET,and TTR gene expression between pancreatic cancer tissues and normal tissues(P<0.05).Surviv-al analysis results showed that MMP1,EPHX2,PLAU,MET,TTRgenes had statistically significant differences between the low expression group and the high expression group in pancreatic cancer(P<0.05).The results of in vitroexperiments showed that the survival rate of pancreatic cancer cells was decreased with the in-crease of emodin concentration(P<0.05).Compared with the normal control group,the mRNA expression levels of PLAU,MMP1,MET,EPHX2genes in the 20 umol/LEmo group and 40 umol/LEmo group were increased,and the expression level of EPHX2 protein was increased(all P<0.05).Conclusion:EPHX2may be the target of emodin in pancreatic cancer.关键词
大黄素/胰腺癌/环氧化物水解酶2/生物信息学Key words
emodin/pancreatic cancer/epoxide hydrolase 2/bioinformatics分类
医药卫生引用本文复制引用
卢洁霞,谢春晓,陈凤平,韦大福,姜海行,覃山羽..基于生物信息学及体外实验研究大黄素治疗胰腺癌的靶点[J].广西医科大学学报,2023,40(12):1964-1971,8.基金项目
国基自然科学基金资助项目(No.81960439) (No.81960439)
广西研究生教育创新计划项目(No.YCSW2023227) (No.YCSW2023227)