| 摘要: |
| 目的：采用网络药理学方法系统揭示雷公藤甲素治疗肝癌的作用机制。方法：分析雷公藤甲素的分子特性以及成药性参数，预测雷公藤甲素治疗肝癌的靶点，筛选并构建雷公藤甲素抗肝癌靶点网络及靶点相互作用网络；对靶点进行基因本体（gene ontology，GO）功能和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析。结果：共筛选出雷公藤甲素59个潜在作用靶点，其中丝氨酸/苏氨酸蛋白激酶1（RAC-alpha serine/threonine-protein kinase，AKT1）、肿瘤蛋白P53（cellular tumor antigen p53，TP53）、Myc原癌基因蛋白（Myc proto-oncogene protein，MYC）、胱天蛋白酶3（cysteine aspartic acid specific protease 3，CASP3）、信号传导与转录激活因子3（signal transducer and activator of transcription 3，STAT3）、血管内皮生长因子A（vascular endothelial growth factor A，VEGFA）等21个靶点为关键靶点；GO功能和KEGG信号通路富集主要涉及细胞凋亡和激酶调控等多条信号通路。结论：本研究从系统生物学角度阐明雷公藤甲素抗肝癌的作用机制，为其作为II型肝癌先导化合物开发提供了参考。 |
| 关键词: 雷公藤甲素 肝癌 成药性预测 作用靶点 信号通路 网络药理学 |
| DOI： |
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| Mechanism of action of triptolide in treatment of liver cancer：A study based on network pharmacology |
| LIU Hequn,WANG Yikun,GUAN Yan |
| (The Second Affiliated Hospital of Hunan University of Chinese Medicine，Changsha 410005，Hunan，China;Xiangya School of Pharmaceutical Sciences，Central South University，Changsha 410013，Hunan，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of triptolide in the treatment of liver cancer based on network pharmacology.Methods：The molecular properties and druggability parameters of triptolide were analyzed，and the targets of triptolide in the treatment of liver cancer were predicted.A target network and a target interaction network were constructed for triptolide in the treatment of liver cancer.Gene ontology （GO）functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG）pathway enrichment analysis were performed for the targets.Results：A total of 59 potential action targets were obtained for triptolide，with 21 core targets including RAC-alpha serine/threonine-protein kinase，cellular tumor antigen p53，Myc proto-oncogene protein，cysteine aspartic acid specific protease 3，signal transducer and activator of transcription 3，and vascular endothelial growth factor A.The GO functional enrichment analysis and KEGG pathway enrichment analysis showed the involvement of multiple signaling pathways such as cell apoptosis and kinase regulation.Conclusion：This study clarifies the mechanism of action of triptolide in the treatment of liver cancer from the perspective of systems biology，which provides a reference for developing type II lead compounds for liver cancer. |
| Key words: triptolide liver cancer druggability prediction action target signaling pathway network pharmacology |
