川龙抑癌汤治疗前列腺癌的作用机制探讨

Mechanism of Chuanlong Anti-cancer Decoction in treatment of prostate cancer

  • 摘要:
      目的  基于网络药理学探讨川龙抑癌汤治疗前列腺癌的作用机制。
      方法  通过TCMSP数据库筛选灵芝、莪术、红花、三七粉、大青叶的有效成分,利用PubChem、Swiss ADME在线网站筛选川足、地龙的有效成分,并通过SwissTargetPrediction在线网站预测上述中药活性成分的潜在靶点,利用GeneCards、OMIM、PharmGkb数据库检索出前列腺癌的相关靶点,运用Venn在线软件获取川龙抑癌汤与前列腺癌的共同靶点,通过Cytoscape 3.8.2软件构建“主要成分-交集靶点”网络图,使用STRING数据库绘制交集靶点的蛋白互作(PPI)网络,利用Hiplot在线工具对有效作用靶点进行基因本体(GO)功能分析、京都基因和基因组百科全书(KEGG)通路富集分析,运用分子对接技术对主要活性成分与关键靶点进行分子对接。
      结果  共获得川龙抑癌汤活性成分149个,川龙抑癌汤与前列腺癌的交集靶点486个,关键靶点包括蛋白激酶(AKT1)、甘油醛-3-磷酸脱氢酶(GAPDH)、肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、基质金属蛋白酶-9(MMP9)、细胞肿瘤抗原基因(TP53)、前列腺素内过氧化物合酶2(PTGS2)和血管内皮生长因子A(VEGFA)等,主要成分包括槲皮素、姜黄素和β-谷甾醇等,GO功能分析主要包括转录因子活性、酶活性、受体活性及生物合成过程的调控等方面。KEGG通路分析涉及癌症蛋白聚糖通路、糖尿病并发症中的晚期糖基化终产物及其受体(AGE-RAGE)信号通路、C型凝集素受体信号通路、缺氧诱导因子1(HIF-1)信号通路、TNF信号通路、白细胞介素-17(IL-17)信号通路、程序性细胞死亡蛋白-1/程序性死亡配体-1(PD-1/PD-L1)通路及前列腺癌等癌症通路,分子对接结果显示主要活性成分与关键靶点之间具有很好的结合性。
      结论  川龙抑癌汤治疗前列腺癌的作用是多成分、多靶点、多通路的,本研究为后续的分子生物学实验提供了理论基础。

     

    Abstract:
      Objective  To explore the action mechanism of Chuanlong Anti-cancer Decoction in treatment of prostate cancer based on network pharmacology.
      Methods  The active components of Lingzhi, Ezhu, Honghua, Sanqi power, Daqingye were screened by TCMSP database. The active components of scolopendra and lumbricus were screened by PubChem and Swiss ADME, and the potential targets of the above active components were predicted by SwissTargetPrediction online website. GeneCards, OMIM and PharmGkb databases were used to retrieve the related targets of prostate cancer. Venn online software was used to obtain the common targets of Chuanlong Anti-cancer Decoction and prostate cancer. Cytoscape 3.8.2 software was used to construct the network diagram of "main component-intersection target". The protein interaction (PPI) network of intersection targets was plotted using STRING database. Hiplot online tool was used to analyze effective targets based on gene ontology(GO) function and KyotoEncyclopedia of Genes and Genomes (KEGG) pathway enrichment, and molecular docking technology was used to conduct molecular docking between main active ingredients and key targets.
      Results  A total of 149 active components of Chuanlong Anti-cancer Decoction and 486 intersection targets of Chuanlong Anti-cancer Decoction and prostate cancer were obtained. The key targets included protein kinase B (AKT1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tumor necrosis factor (TNF), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP9), cell tumor antigen gene (TP53), prolandin endoperoxidase synthase 2 (PTGS2) and vascular endothelial growth factor A (VEGFA), etc., and the main components included quercetin, curcumin and β-sitosterol, etc. GO function analysis mainly included transcription factor activity, enzyme activity, receptor activity and regulation of biosynthesis process. KEGG pathway analysis involved in cancer proteoglycan pathway, advanced glycation end product (AGE)-receptor for AGE (RAGE) signaling pathway in late-stage complications of diabetes, C-type lectin receptor signaling pathway, hypoxia-inducible factor 1 (HIF-1) signaling pathway, tumor necrosis factor (TNF) signaling pathway, interleukin-17 (IL-17) signaling pathway, programmed cell death protein-1/programmed death ligand 1 (PD-1/PD-L1) pathway and prostate cancer pathways, etc. Molecular docking results showed good binding between the main active ingredients and key targets.
      Conclusion  The effect of Chuanlong Anti-cancer Decoction involves in multi-components, multi-targets and multi-pathways during treatment of prostate cancer, which provides a theoretical basis for subsequent molecular biology experiments.

     

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