The Potential Mechanism of Dihydroartemisinin in the Treatment of Thyroid Cancer Through Network Pharmacological Analysis

Background: Thyroid cancer (THCA) has recently become one of the most common endocrine malignancies worldwide. Dihydroartemisinin (DHA) exhibits well-documented antitumor activity, but its therapeutic potential in THCA remains largely unclear. Methods: The relative mRNA and protein expression levels of the apoptosis-related markers Bax, Bcl-2, and Caspase-3 in the human THCA cell line TPC-1 were evaluated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Potential active targets of DHA were obtained from the TCMSP, SwissTargetPrediction and SuperPred databases. The THCA-related targets were collected from TCGA, DisGeNET and GeneCards. Protein–protein interaction (PPI) network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to predict key targets and pathways of DHA against THCA. Results: DHA treatment significantly modulated the expression of apoptosis-related markers, including upregulation of Bax and Caspase-3 and downregulation of Bcl-2, suggesting that DHA may promote apoptosis in TPC-1 cells. A total of 230 potential targets were identified from the overlap between DHA- and THCA-related targets. Indeed, STAT3, PIK3R1, PIK3CA, PIK3CD, MAPK1, MAPK3, EGFR, HSP90AA1, ESR1, PTPN11 were identified as the top 10 hub genes. In total, 2214 biological processes, 118 cellular components, and 220 molecular functions were enriched. KEGG analysis indicated that DHA may suppress THCA primarily via the chemical carcinogenesis-receptor activation pathway. Conclusion: These findings suggest that DHA is a promising candidate for THCA treatment and warrant further investigation, including direct apoptosis assays and in vivo validation.