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基于表达谱的Zunyimycin C抗肝细胞癌的机制分析

Mechanism Analysis of Zunymycin C Against Hepatocellular Carcinoma Based on Expression Profiles
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摘要 目的 探讨蒽酮类抗生素Zunyimycin C治疗肝细胞癌(HCC)的作用机制。方法 通过PharmGKB网络药理学工具预测Zunyimycin C抗HCC的作用靶点;以Zunyimycin C干预HCC HepG2和人源正常肝细胞L02,分为试剂处理组、空白对照组、药物处理组及药物处理后加抑制剂组。对不同处理组进行基因测序分析,筛选差异性表达基因,运用在线数据库进行京都基因与基因组百科全书(KEGG)富集分析,根据基因表达谱进行聚类分析。结果 预测得到细胞内与Zunyimycin C结合得分最高的20个靶点,这些靶点主要参与代谢和肿瘤发生发展的通路。KEGG通路富集分析表明,癌症、磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)、RAS相关蛋白(Rap1)、细胞黏附分子、焦点黏附、丝裂原活化蛋白激酶(MAPK)是Zunyimycin C发挥抗HCC的主要通路。结论 Zunyimycin C可能是通过多靶点多通路的方式发挥抗肿瘤作用。 Objective To explore the mechanism of anthrone antibiotic Zunymycin C in the treatment of hepatocellular carcinoma(HCC).Methods The targets of Zunyimycin C against HCC were predicted by PharmGKB network pharmacological tool.HCC cell HepG2 and human normal hepatocellular cell L02 intervened with Zunymycin C were divided into reagent treatment group,blank control group,drug treatment group,and drug treatment plus inhibitor group.Gene sequencing analysis was performed in each group to screen for differentially expressed genes.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis was performed using an online database,and clustering analysis was performed based on gene expression profiles.Results The top 20 targets with the highest score of intracellular binding to zunyimycin C were predicted,which were mainly involved in metabolic and tumor development pathways.KEGG pathway enrichment analysis showed that cancer,phosphatidylinositol 3-kinase protein kinase B(PI3K-Akt),RAS related protein(Rap1),cell adhesion molecules,focal adhesion,and mitogen activated protein kinase(MAPK)were the main pathways through which Zunymycin C exerted its anti-HCC effects.Conclusion Zunymycin C may exert anti-tumor effects through multiple targets and pathways.
作者 张桢淳 栗午娟 郭雨悦 李振豪 王卓灵 孙心悦 吕玉红 岳昌武 Zhang Zhenchun;Li Wujuan;Guo Yuyue;Li Zhenhao;Wang Zhuoling;Sun Xinyue;Lv Yuhong;Yue Changwu(Yan'an Key Laboratory of Microbial Drug Innovation and Transformation·Medical School of Yan'an University,Yan'an 716000,China)
出处 《成都医学院学报》 CAS 2024年第2期220-224,236,共6页 Journal of Chengdu Medical College
基金 国家自然科学基金项目(No:81860653) 国家级大学生创新创业训练计划(No:202210719026)。
关键词 Zunyimycin C 肝细胞癌 网络药理学 Zunyimycin C Hepatocellular carcinoma Network pharmacology
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