结合网络药理学与实验验证探索脱氧土大黄苷（DET）对非小细胞肺癌（NSCLC）的抑制作用。

Combining network pharmacology and experimental verification to explore the inhibitory effects of Deoxyelephantopin (DET) Against Non-Small Cell Lung Cancer (NSCLC).

作者信息

Wu Shenjia, Guo Ying, Wang Rong

机构信息

School of Biology and Food Engineering, Fuyang Normal University, Fuyang Anhui, 236041, China.

Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, 100 Qinghe West Road, Fuyang Anhui, 236041, China.

出版信息

BMC Cancer. 2025 Apr 21;25(1):738. doi: 10.1186/s12885-025-14066-3.

DOI:10.1186/s12885-025-14066-3

PMID:40259252

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12010628/

Abstract

BACKGROUND

DET has a significant inhibitory activity against a range of cancer cells; however, its specific effects and underlying mechanisms in Non-Small Cell Lung Cancer (NSCLC) remain to be fully elucidated. This study aimed to investigate the potential mechanisms through which DET exerts its anti-neoplastic effects on NSCLC.

METHOD

Targets of DET were predicted using the SwissTargetPrediction database. Disease targets for NSCLC were obtained from the GeneCards database, and the intersection between drug targets and disease targets was determined. The STRING database was then employed to construct a protein-protein interaction (PPI) network and analyze target interactions. Additionally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG)enrichment analyses were conducted to investigate their biological functions. Molecular docking simulations were conducted using AutoDock software to analyze the binding interactions between DET and key target proteins. Subsequently, both in vitro and in vivo experiments were carried out to evaluate the anticancer effects of DET, with alterations in key gene expression levels assessed through RT-qPCR and Western blot analyses.

RESULTS

A total of 52 potential targets were discovered for DET and NSCLC. The PPI analysis revealed 5 hub targets, including CASP3, PTGS2, TNFα, ICAM1 and JUN. GO analysis identified 164 biological processes, 44 molecular functions and 40 cellular components. KEGG analysis revealed that DET anticancer effects were mediated through multiple pathways, primarily the AGE-RAGE and TNF signaling pathways. Experimental results demonstrated that DET inhibited the proliferation and migration of H460 cells and induced apoptosis in vitro. RT-qPCR and WB indicated that DET up regulated Bax and CASP3 while down regulating Bcl2, JUN, TNFα, NF-κB, ICAM1 and PTGS2.

CONCLUSION

This study aims to investigate the inhibitory effect of DET on NSCLC by combining network pharmacology and experimental methods. The results demonstrate that DET effectively inhibited the proliferation of H460 cells and induced apoptosis, with significant involvement of the AGE-RAGE and TNF signaling pathways, suggesting its potential as a therapeutic intervention for NSCLC.

摘要

背景

DET 对多种癌细胞具有显著的抑制活性；然而，其在非小细胞肺癌（NSCLC）中的具体作用及潜在机制仍有待充分阐明。本研究旨在探究 DET 对 NSCLC 发挥抗肿瘤作用的潜在机制。

方法

使用 SwissTargetPrediction 数据库预测 DET 的靶点。从 GeneCards 数据库获取 NSCLC 的疾病靶点，并确定药物靶点与疾病靶点的交集。然后利用 STRING 数据库构建蛋白质-蛋白质相互作用（PPI）网络并分析靶点相互作用。此外，进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析以研究其生物学功能。使用 AutoDock 软件进行分子对接模拟，以分析 DET 与关键靶点蛋白之间的结合相互作用。随后，进行体外和体内实验以评估 DET 的抗癌效果，并通过 RT-qPCR 和蛋白质印迹分析评估关键基因表达水平的变化。

结果

共发现 DET 和 NSCLC 的 52 个潜在靶点。PPI 分析揭示了 5 个枢纽靶点，包括 CASP3、PTGS2、TNFα、ICAM1 和 JUN。GO 分析确定了 164 个生物学过程、44 个分子功能和 40 个细胞成分。KEGG 分析表明，DET 的抗癌作用是通过多种途径介导的，主要是 AGE-RAGE 和 TNF 信号通路。实验结果表明，DET 在体外抑制 H460 细胞的增殖和迁移并诱导凋亡。RT-qPCR 和 WB 表明，DET 上调 Bax 和 CASP3，同时下调 Bcl2、JUN、TNFα、NF-κB、ICAM1 和 PTGS2。