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

作　　者：孙志婷 杨慧[1] 孟令偿 吴静[1] 穆耕林 SUN Zhiting;YANG Hui;MENG Lingchang;WU Jing;MU Genglin(Institute of Chinese Medicine,Nanjing University,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]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

出　　处：《世界中医药》2024年第14期2081-2090,共10页World Chinese Medicine

基　　金：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)。

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。Objective: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.

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 

分 类 号：R285.5[医药卫生—中药学]