Network pharmacological mechanism and molecular experimental validation of artemisinin in the treatment of lung adenocarcinoma

IF 3.3 3区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicology and applied pharmacology Pub Date : 2025-02-01 DOI:10.1016/j.taap.2025.117226

Zhimin Lu , Jialu Jiang , Xuming Yao , Guoxin Hou

{"title":"Network pharmacological mechanism and molecular experimental validation of artemisinin in the treatment of lung adenocarcinoma","authors":"Zhimin Lu , Jialu Jiang , Xuming Yao , Guoxin Hou","doi":"10.1016/j.taap.2025.117226","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer is a medical ailment with high mortality and prevalence rates. Artemisinin (ART) and its derivatives exhibit anti-cancer properties against various malignancies, including lung cancer. However, further research is required to determine the precise anti-cancer mechanisms of ART. Hence, this study aimed to utilize network pharmacology to preliminarily investigate the therapeutic effectiveness and mode of action of this medication.</div></div><div><h3>Methods</h3><div>Using a bioinformatics approach, five target proteins with the strongest connections were selected for docking. Gene enrichment analysis was performed, and the ART target proteins were predicted. Various methods, including methyl thiazolyl tetrazolium (MTT) assays, colony formation assays, microsphere formation assays, flow cytometry, and western blotting analysis, were employed to assess the impact of ART on the malignant characteristics of lung cancer cells.</div></div><div><h3>Results</h3><div>Bioinformatic analysis identified 51 ART target genes in lung adenocarcinoma for further analysis. Pathway enrichment analysis of target genes revealed 639 enriched Gene Ontology-Biological Process (GO BP) and 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These findings imply that ART may control the IL-6 signaling pathway by focusing on important molecules such as CDK4 and IL-6. The ART-treated group experienced apoptosis induction, cell cycle arrest, and inhibition of cell proliferation and microsphere formation compared with the control group (<em>p</em> < 0.05, <em>p</em> < 0.01). Additionally, ART reduced the protein expression of CDK4, COX2, ERBB2, CD44, and EpCAM while increasing that of caspase 3, IL-6, p53, and SRC (<em>p</em> < 0.01).</div></div><div><h3>Conclusion</h3><div>ART inhibited the growth and stemness of HCC827 cells.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"495 ","pages":"Article 117226"},"PeriodicalIF":3.3000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology and applied pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0041008X2500002X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Lung cancer is a medical ailment with high mortality and prevalence rates. Artemisinin (ART) and its derivatives exhibit anti-cancer properties against various malignancies, including lung cancer. However, further research is required to determine the precise anti-cancer mechanisms of ART. Hence, this study aimed to utilize network pharmacology to preliminarily investigate the therapeutic effectiveness and mode of action of this medication.

Methods

Using a bioinformatics approach, five target proteins with the strongest connections were selected for docking. Gene enrichment analysis was performed, and the ART target proteins were predicted. Various methods, including methyl thiazolyl tetrazolium (MTT) assays, colony formation assays, microsphere formation assays, flow cytometry, and western blotting analysis, were employed to assess the impact of ART on the malignant characteristics of lung cancer cells.

Results

Bioinformatic analysis identified 51 ART target genes in lung adenocarcinoma for further analysis. Pathway enrichment analysis of target genes revealed 639 enriched Gene Ontology-Biological Process (GO BP) and 17 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These findings imply that ART may control the IL-6 signaling pathway by focusing on important molecules such as CDK4 and IL-6. The ART-treated group experienced apoptosis induction, cell cycle arrest, and inhibition of cell proliferation and microsphere formation compared with the control group (p < 0.05, p < 0.01). Additionally, ART reduced the protein expression of CDK4, COX2, ERBB2, CD44, and EpCAM while increasing that of caspase 3, IL-6, p53, and SRC (p < 0.01).

Conclusion

ART inhibited the growth and stemness of HCC827 cells.

查看原文本刊更多论文

青蒿素治疗肺腺癌的网络药理机制及分子实验验证。

背景：肺癌是一种死亡率和患病率都很高的内科疾病。青蒿素（ART）及其衍生物对包括肺癌在内的多种恶性肿瘤具有抗癌作用。然而，需要进一步的研究来确定抗逆转录病毒治疗的确切抗癌机制。因此，本研究旨在利用网络药理学对该药物的治疗效果和作用方式进行初步探讨。方法：采用生物信息学方法，选择连接最强的5个靶蛋白进行对接。进行基因富集分析，并预测ART靶蛋白。采用多种方法，包括甲基噻唑四氮唑（MTT）测定、菌落形成测定、微球形成测定、流式细胞术和western blotting分析，评估ART对肺癌细胞恶性特征的影响。结果：生物信息学分析鉴定出51个ART靶基因用于肺腺癌的进一步分析。通路富集分析发现639条富集的基因本体-生物过程（GO BP）通路和17条富集的京都基因与基因组百科全书（KEGG）通路。这些发现暗示ART可能通过聚焦CDK4和IL-6等重要分子来控制IL-6信号通路。与对照组相比，ART治疗组细胞凋亡诱导、细胞周期阻滞、细胞增殖和微球形成受到抑制（p ）。结论：ART可抑制HCC827细胞的生长和干性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Toxicology and applied pharmacology 医学-毒理学

CiteScore

6.80

自引率

2.60%

发文量

309

审稿时长

32 days

期刊介绍： Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.