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基于网络药理学的多西他赛治疗绒毛膜癌的作用机制研究

Mechanism of docetaxel in treatment of choriocarcinoma based on network pharmacology

    摘要
  • 摘要:
      目的  基于网络药理学探讨多西他赛治疗绒毛膜癌的作用靶点及信号通路。
      方法  通过Genecards数据库收集多西他赛、绒毛膜癌的靶点。对绒毛膜癌疾病靶点以及多西他赛药物靶点进行映射，构建作用靶点的蛋白质互作(PPI)网络模型，筛选出排名前10的Hub基因。采用Cytoscape软件建立药物-疾病靶点的网络模型。利用DAVID数据库进行基因本体论(GO)功能富集分析和京都基因和基因组百科全书(KEGG)信号通路富集分析。
      结果  多西他赛、绒毛膜癌靶点分别为953、1 137个，多西他赛治疗绒毛膜癌的关键靶点包括TP53、AKT1、CASP8、STAT3等，涉及的主要KEGG通路富集分析确定信号通路包括癌症通路、细胞凋亡通路、Focal Adhesion通路、p53信号通路等。
      结论  多西他赛治疗绒毛膜癌是通过调节TP53、AKT1、STAT3等关键基因来调控癌症通路、细胞凋亡通路、p53信号通路等信号通路实现的。

     

    Abstract:
      Objective  To explore the action target and signal pathway of docetaxel in treatment of choriocarcinoma based on network pharmacology.
      Methods  The targets of docetaxel and choriocarcinoma were collected from Genecards database. The disease targets of choriocarcinoma and docetaxel drug targets were mapped, the protein-protein interaction (PPI) network model of target was constructed, and the top 10 hub genes were screened. The network model of drug-disease targets was established by Cytoscape software. DAVID database was used for gene ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway enrichment analysis.
      Results  A total of 953 and 1 137 targets were found for docetaxel and choriocarcinoma respectively, the key targets of docetaxel in the treatment of choriocarcinoma included TP53, AKT1, CASP8, STAT3 and etc. Determined signal paths found by KEGG pathway enrichment analysis involved cancer pathway, apoptosis pathway, Focal Adhesion pathway, p53 and other signaling pathways.
      Conclusion  Docetaxel treating choriocarcinoma is achieved by regulating key genes such as TP53, AKT1 and STAT3 to regulate signaling pathways such as cancer pathway, apoptosis pathway and p53 pathway.

     

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