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

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, COX-2, ERBB2, CD44, and EpCAM while increasing that of caspase3, IL-6, P-53, and SRC (p < 0.01).

Conclusion: ART inhibited the growth and stemness of HCC827 cells.