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
分子伴侣热休克蛋白90(heat shock protein 90,HSP90)能够通过泛素化途径保护细胞内蛋白质功能,其在肿瘤细胞中呈过表达状态,维持肿瘤细胞生长、增殖、抗凋亡及转移能力。Ganetespib是目前广泛应用于多种肿瘤治疗临床试验的小分子HSP90...分子伴侣热休克蛋白90(heat shock protein 90,HSP90)能够通过泛素化途径保护细胞内蛋白质功能,其在肿瘤细胞中呈过表达状态,维持肿瘤细胞生长、增殖、抗凋亡及转移能力。Ganetespib是目前广泛应用于多种肿瘤治疗临床试验的小分子HSP90抑制剂,其单药具有高效能的抗肿瘤活性,联合用药能增强标准化疗或其他靶向治疗疗效,且能同时克服多种肿瘤的耐药机制,本文就Ganetespib在多种人类恶性实体肿瘤治疗中的疗效进行讨论。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.
文摘分子伴侣热休克蛋白90(heat shock protein 90,HSP90)能够通过泛素化途径保护细胞内蛋白质功能,其在肿瘤细胞中呈过表达状态,维持肿瘤细胞生长、增殖、抗凋亡及转移能力。Ganetespib是目前广泛应用于多种肿瘤治疗临床试验的小分子HSP90抑制剂,其单药具有高效能的抗肿瘤活性,联合用药能增强标准化疗或其他靶向治疗疗效,且能同时克服多种肿瘤的耐药机制,本文就Ganetespib在多种人类恶性实体肿瘤治疗中的疗效进行讨论。
