Lu Zhimin, Jiang Jialu, Yao Xuming, Hou Guoxin
Department of Outpatient, Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China.
Department of Oncology, Affiliated Hospital of Jiaxing University, The First Hospital of Jiaxing, Jiaxing, Zhejiang, China.
Toxicol Appl Pharmacol. 2025 Feb;495:117226. doi: 10.1016/j.taap.2025.117226. Epub 2025 Jan 6.
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.
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.
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).
ART inhibited the growth and stemness of HCC827 cells.
肺癌是一种死亡率和发病率都很高的疾病。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特性。然而，需要进一步研究以确定青蒿素确切的抗癌机制。因此，本研究旨在利用网络药理学初步探究该药物的治疗效果和作用方式。
采用生物信息学方法，选择连接性最强的5种靶蛋白进行对接。进行基因富集分析，并预测青蒿素的靶蛋白。采用多种方法，包括甲基噻唑基四氮唑（MTT）法、集落形成试验、微球形成试验、流式细胞术和蛋白质印迹分析，来评估青蒿素对肺癌细胞恶性特征的影响。
生物信息学分析确定了肺腺癌中51个青蒿素靶基因以供进一步分析。靶基因的通路富集分析揭示了639个富集的基因本体生物学过程（GO BP）和17个富集的京都基因与基因组百科全书（KEGG）通路。这些发现表明，青蒿素可能通过聚焦于细胞周期蛋白依赖性激酶4（CDK4）和白细胞介素-6（IL-6）等重要分子来控制IL-6信号通路。与对照组相比，青蒿素处理组出现凋亡诱导、细胞周期阻滞，并抑制细胞增殖和微球形成（p < 0.05，p < 0.01）。此外，青蒿素降低了CDK4、环氧化酶2（COX2）、表皮生长因子受体2（ERBB2）、CD44和上皮细胞黏附分子（EpCAM）的蛋白表达，同时增加了半胱天冬酶3、IL-6、p53和肉瘤蛋白（SRC）的表达（p < 0.01）。
青蒿素抑制了HCC827细胞的生长和干性。
