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The Anti-Tumor Mechanism and Target of Triptolide Based on Network Pharmacology and Molecular Docking
Recent Patents on Anti-Cancer Drug Discovery ( IF 2.5 ) Pub Date : 2021-07-31 , DOI: 10.2174/1574892816666210211143059
Tao Zou 1 , Yuanqiong Huang 2 , Yifan Hu 1 , Mingyu Wu 1 , Yueshui Zhao 1 , Fukuan Du 1 , Mingxing Li 1 , Xu Wu 1 , Huijioa Ji 1 , Parham Jabbarzadeh Kaboli 1 , Shurong Wang 3 , Zhangang Xiao 1 , Zhigui Wu 3
Affiliation  

Background: According to the special physiological and pharmacological activities of natural compounds, many drugs with special therapeutic effects have been developed. The Triptolide (TP) is a natural anti-tumor drug with a world patent, but its target and mechanism are yet unknown.

Objective: The study aims to explore and predict the target and mechanism of TP on Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PC) and Colorectal Cancer (CC) through network pharmacology technology.

Methods: We screened the core targets of TP with NSCLC, PC and CC, respectively, and carried out network analysis, enrichment analysis and ligand-receptor docking to clarify its potential pharmacological mechanism.

Results: By screening the core genes between TP with NSCLC, PC and CC, respectively, it was found that PTGS2 was the common target gene in the three cancers. NSCLC, CCL2, IL6, HMOX1 and COL1A1 are the specific target genes, while MMP2, JUN, and CXCL8 are the specific target genes in PC. In CC, the specific target genes includeERBB2, VEGFA, STAT1 and MAPK8. In enrichment analysis, it was found that the NF- κB, toll-like receptors and IL-17 signaling pathway were mainly involved in TP for these cancers. The binding energy of TP to the core target is less than that of cyclophosphamide.

Conclusion: This study preliminarily revealed that TP may prevent and treat cancers\ through multiple targets and pathways. The possible mechanisms of TP include regulating immune and inflammatory responses, promoting apoptosis and inhibiting tumor development. It shows that TP may have potential in treating kinds of tumors.



中文翻译:

基于网络药理学和分子对接的雷公藤内酯类抗肿瘤机制及靶点

背景:根据天然化合物的特殊生理和药理活性,已开发出许多具有特殊治疗作用的药物。雷公藤内酯(TP)是一种具有世界专利的天然抗肿瘤药物,但其作用靶点和作用机制尚不清楚。

目的:本研究旨在通过网络药理学技术探索和预测TP治疗非小细胞肺癌(NSCLC)、胰腺癌(PC)和结直肠癌(CC)的靶点和作用机制。

方法:我们分别筛选出TP与NSCLC、PC和CC的核心靶点,进行网络分析、富集分析和配体-受体对接,阐明其潜在的药理作用机制。

结果:通过分别筛选TP与NSCLC、PC和CC的核心基因,发现PTGS2是三种癌症的共同靶基因。NSCLC、CCL2、IL6、HMOX1和COL1A1是PC的特异性靶基因,而MMP2、JUN和CXCL8是PC的特异性靶基因。在CC中,特异性靶基因包括ERBB2、VEGFA、STAT1和MAPK8。在富集分析中发现,NF-κB、toll样受体和IL-17信号通路主要参与了这些癌症的TP。TP与核心靶点的结合能小于环磷酰胺。

结论:本研究初步揭示TP可通过多靶点和多途径防治癌症。TP的可能机制包括调节免疫和炎症反应、促进细胞凋亡和抑制肿瘤发展。这表明TP可能具有治疗多种肿瘤的潜力。

更新日期:2021-07-31
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