世界中医药
文章摘要
引用本文:孙志婷,杨慧,孟令偿,吴静,穆耕林.基于生物信息学和体外实验探讨紫草素潜在的抗肿瘤机制[J].世界中医药,2024,(14):.  
基于生物信息学和体外实验探讨紫草素潜在的抗肿瘤机制
Potential Mechanism of Shikonin in Treatment of Cancer Based on Bioinformatics and in Vitro Experiments
投稿时间:2023-08-25  
DOI:10.3969/j.issn.1673-7202.2024.14.006
中文关键词:  生物信息学  紫草素  肝癌  前列腺癌  结肠癌  靶点  细胞凋亡
English Keywords:Bioinformatics  Shikonin  Hepatocellular carcinoma  Prostate adenocarcinoma  Colon adenocarcinoma  Targets  Cell apoptosis
基金项目:国家自然科学基金青年科学基金项目(82204720);中央高校基本科研业务费专项(3332022084);2023年南京市卫生科技发展专项资金项目(YKK23090)
作者单位
孙志婷,杨慧,孟令偿,吴静,穆耕林 南京大学中医研究院南京大学医学院附属鼓楼医院南京210008 
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中文摘要:
      目的:紫草素(SHK),一种紫草根部的萘醌类活性成分,具有抗肿瘤活性。本研究通过生物信息学方法和细胞实验,探索SHK在肝细胞肝癌(LIHC)、前列腺腺癌(PRAD)和结肠腺癌(COAD)中的新靶点。方法:通过人类基因数据库(GeneCard)及癌症基因图谱(TCGA)获得SHK与3种癌症的交集基因,并进行基因本体(GO)和京都基因和基因组百科全书(KEGG)富集分析、蛋白质-蛋白质相互作用(PPT)网络构建等。体外实验检测SHK对人肝癌细胞(HepG2)、人前列腺癌细胞(LNCaP C4-2)和人结肠癌细胞(HT-29)的抑制作用,并分析SHK对细胞凋亡及预测靶点基因表达的影响。结果:SHK显著抑制3种癌细胞增殖并通过调节周期素依赖性激酶抑制因子1A(CDKN1A)等基因的表达实现抗肿瘤作用,且与生物信息学预测结果一致。此外,Kaplan-Meier生存曲线进一步表明CDKN1A等是SHK影响癌症患者生存的重要靶点;CDKN1A和B淋巴细胞瘤-2(BCL-2)是SHK抑制肿瘤细胞增殖和侵袭的核心靶点。结论:SHK可通过人体抑癌基因(P53)/CDKN1A和BCL-2/BCL-2关联X蛋白(BAX)通路诱导癌细胞凋亡。本研究报道了SHK抑制肿瘤的作用靶点及潜在机制,为含SHK的中草药作为抗肿瘤的潜在药物提供了初步依据。
English Summary:
      Shikonin(SHK),a naphthoquinone pigment-type active ingredient of lithospermum root,has anti-tumor activity.This study aims to identify novel targets of SHK in hepatocellular carcinoma(LIHC),prostate adenocarcinoma(PRAD),and colon adenocarcinoma(COAD) using bioinformatics methods and in vitro experiments.Methods:Intersection genes of SHK and three kinds of cancer were screened from GeneCard and TCGA databases.Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analyses and protein-protein interaction(PPT) network construction were performed.The study detected the inhibitory effect of SHK on HepG2,LNCaP C4-2,and HT-29 cells through in vitro experiments and analyzed the effect of SHK on cell apoptosis and expression of predicted target genes.Results:SHK significantly inhibited the proliferation of three kinds of cancer cells and achieved the anti-tumor effect by regulating the expression of CDKN1A and other genes,which was consistent with the prediction of bioinformatics.In addition,the Kaplan-Meier survival curve further showed that CDKN1A and other genes were important targets of SHK affecting the survival of patients with cancer.CDKN1A and BCL-2 were the core targets of SHK in inhibiting the proliferation and invasion of cancer cells.Conclusion:SHK may induce cancer cell apoptosis through the P53/CDKN1A and BCL-2/BAX signaling pathways.The study reports the anti-tumor targets and underlying mechanisms of SHK,which provides preliminary evidence for the application of SHK-containing Chinese herbal medicine as a potential anti-tumor drug.
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