Beishashen(BSS)and Maidong(MD)are commonly used Medicine right for the treatment of non-small cell lung cancer(NSCLC),but their specific mechanism of action is not clear.In this study,network pharmacology and molecula...Beishashen(BSS)and Maidong(MD)are commonly used Medicine right for the treatment of non-small cell lung cancer(NSCLC),but their specific mechanism of action is not clear.In this study,network pharmacology and molecular docking techniques were used to investigate the molecular mechanisms of the therapeutic effects of BSS-MD on NSCLC and to experimentally validate some of the targets.The network pharmacology approach,including active ingredient and target screening,drug-compound-target network construction,protein-protein interaction(PPI)network,enrichment analysis,and molecular docking,was used to investigate the mechanism of action of Beisashen and Maitong on NSCLC.First,the active components of BSS-MD and their targets were predicted,of which 423 targets interacted with NSCLC targets.Then,network pharmacology showed that Stigmasterol,Quercetin,Alloisoimperatorin,Isoimperatorin,Beta-sitosterol were the core components of BSS-MD,and PLK1,HSP90AB1,and CDK1 were the key therapeutic targets.KEGG enrichment analysis indicated that the mechanism of action of BSS-MD in NSCLC treatment was related to the cell cycle.Then we further performed experimental validation.CCK-8 assay showed that BSS-MD inhibited LEWIS cell viability and promoted apoptosis in a dose-dependent manner.qPCR assay,immunofluorescence,and protein blotting experiments demonstrated that compared with the control group and the control group,the expression of PLK1,HSP90AB1,and CDK1 mRNAs and proteins were reduced in the treatment group(P<0.01).Therefore,we conclude that BSS-MD can block cell cycle progression by inhibiting the expression of PLK1,CDK1,and HSP90AB1 mRNAs and proteins to inhibit lung cancer cell growth and promote apoptosis,and emphasize that BSS-MD are promising adjuvants for NSCLC treatment.展开更多
目的:运用复杂网络分析技术探讨“北沙参-桔梗”药对治疗放射性肺炎的作用靶点及信号通路。方法:在中药系统药理学数据库与分析平台筛选“北沙参-桔梗”的潜在有效成分及其对应的靶点蛋白;通过人类基因数据库搜索已知与放射性肺炎关联...目的:运用复杂网络分析技术探讨“北沙参-桔梗”药对治疗放射性肺炎的作用靶点及信号通路。方法:在中药系统药理学数据库与分析平台筛选“北沙参-桔梗”的潜在有效成分及其对应的靶点蛋白;通过人类基因数据库搜索已知与放射性肺炎关联的靶基因;采用Cytoscape软件描绘化合物-靶点网络图;将靶基因导入STRING数据平台以描绘蛋白-蛋白相互作用网络(protein-protein interactions,PPI);在R语言环境下对靶点基因进行基因本体论功能富集分析(gene ontology,GO)和KEGG富集分析(kyoto encyclopedia of genes and genomes,KEGG),绘制主要富集结果的柱状图,并根据富集结果探讨“北沙参-桔梗”治疗放射性肺炎的作用机理。结果:共筛选出“北沙参-桔梗”潜在有效成分15个,放射性肺炎靶点基因124个。其中Akt1是PPI网络中最核心靶点,其次分别为白细胞介素6、血管内皮生长因子A、丝裂原活化蛋白激酶1等。GO富集分析共得到132条生物过程;KEGG富集分析得到150条信号通路。重要信号通路涉及TNF信号通路、白细胞介素17信号通路、PI3K-Akt信号通路、HIF-1信号通路、C型凝集素受体信号通路、松弛素信号通路、Toll样受体信号通路、p53信号通路、NF-kappa B信号通路。结论“:北沙参-桔梗”药对在疾病早期具有抗炎作用,晚期具有抗纤维化作用,其治疗作用是多途径、多环节、多靶点的协同作用。展开更多
基金This research was supported by“Zhejiang Province Chinese Medicine Science and Technology Program Key Projects”(No.2021ZZ008).
文摘Beishashen(BSS)and Maidong(MD)are commonly used Medicine right for the treatment of non-small cell lung cancer(NSCLC),but their specific mechanism of action is not clear.In this study,network pharmacology and molecular docking techniques were used to investigate the molecular mechanisms of the therapeutic effects of BSS-MD on NSCLC and to experimentally validate some of the targets.The network pharmacology approach,including active ingredient and target screening,drug-compound-target network construction,protein-protein interaction(PPI)network,enrichment analysis,and molecular docking,was used to investigate the mechanism of action of Beisashen and Maitong on NSCLC.First,the active components of BSS-MD and their targets were predicted,of which 423 targets interacted with NSCLC targets.Then,network pharmacology showed that Stigmasterol,Quercetin,Alloisoimperatorin,Isoimperatorin,Beta-sitosterol were the core components of BSS-MD,and PLK1,HSP90AB1,and CDK1 were the key therapeutic targets.KEGG enrichment analysis indicated that the mechanism of action of BSS-MD in NSCLC treatment was related to the cell cycle.Then we further performed experimental validation.CCK-8 assay showed that BSS-MD inhibited LEWIS cell viability and promoted apoptosis in a dose-dependent manner.qPCR assay,immunofluorescence,and protein blotting experiments demonstrated that compared with the control group and the control group,the expression of PLK1,HSP90AB1,and CDK1 mRNAs and proteins were reduced in the treatment group(P<0.01).Therefore,we conclude that BSS-MD can block cell cycle progression by inhibiting the expression of PLK1,CDK1,and HSP90AB1 mRNAs and proteins to inhibit lung cancer cell growth and promote apoptosis,and emphasize that BSS-MD are promising adjuvants for NSCLC treatment.
文摘目的:运用复杂网络分析技术探讨“北沙参-桔梗”药对治疗放射性肺炎的作用靶点及信号通路。方法:在中药系统药理学数据库与分析平台筛选“北沙参-桔梗”的潜在有效成分及其对应的靶点蛋白;通过人类基因数据库搜索已知与放射性肺炎关联的靶基因;采用Cytoscape软件描绘化合物-靶点网络图;将靶基因导入STRING数据平台以描绘蛋白-蛋白相互作用网络(protein-protein interactions,PPI);在R语言环境下对靶点基因进行基因本体论功能富集分析(gene ontology,GO)和KEGG富集分析(kyoto encyclopedia of genes and genomes,KEGG),绘制主要富集结果的柱状图,并根据富集结果探讨“北沙参-桔梗”治疗放射性肺炎的作用机理。结果:共筛选出“北沙参-桔梗”潜在有效成分15个,放射性肺炎靶点基因124个。其中Akt1是PPI网络中最核心靶点,其次分别为白细胞介素6、血管内皮生长因子A、丝裂原活化蛋白激酶1等。GO富集分析共得到132条生物过程;KEGG富集分析得到150条信号通路。重要信号通路涉及TNF信号通路、白细胞介素17信号通路、PI3K-Akt信号通路、HIF-1信号通路、C型凝集素受体信号通路、松弛素信号通路、Toll样受体信号通路、p53信号通路、NF-kappa B信号通路。结论“:北沙参-桔梗”药对在疾病早期具有抗炎作用,晚期具有抗纤维化作用,其治疗作用是多途径、多环节、多靶点的协同作用。
