Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Department of Nephropathy, Luzhou Traditional Chinese Medicine Hospital, Luzhou 646000, China.
Recent Pat Anticancer Drug Discov. 2021;16(3):426-435. doi: 10.2174/1574892816666210211143059.
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.
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.
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.
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.
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.
根据天然化合物的特殊生理和药理学活性，开发了许多具有特殊治疗效果的药物。雷公藤红素（TP）是一种具有世界专利的天然抗肿瘤药物，但它的靶点和机制尚不清楚。
本研究旨在通过网络药理学技术探讨和预测 TP 对非小细胞肺癌（NSCLC）、胰腺癌（PC）和结直肠癌（CC）的作用靶点和作用机制。
分别筛选 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，阐明其潜在的药理机制。
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 的特异性靶基因有 CCL2、IL6、HMOX1 和 COL1A1，而 PC 的特异性靶基因有 MMP2、JUN 和 CXCL8。在 CC 中，特异性靶基因包括 ERBB2、VEGFA、STAT1 和 MAPK8。在富集分析中发现，TP 主要通过 NF-κB、Toll 样受体和 IL-17 信号通路作用于这些癌症。TP 与核心靶点的结合能小于环磷酰胺。
本研究初步揭示了 TP 可能通过多个靶点和通路预防和治疗癌症。TP 的作用机制可能包括调节免疫和炎症反应、促进细胞凋亡和抑制肿瘤发展。表明 TP 可能在治疗多种肿瘤方面具有潜力。
