Research on the antitumor mechanism of plumbagin to treat differentiated thyroid cancer based on network pharmacology and experimental validation

Objective: Differentiated thyroid carcinoma (DTC) is the most common type of thyroid cancer (TC), accounting for 70% to 80% of all TC cases. However, 10% to 15% of DTC patients experience neoplasm metastasis and recurrence. Plumbagin is a bioactive molecule that inhibits the formation of neoplastic cells by inactivating signal pathways. Methods: We investigated the antitumor activity of plumbagin in DTC and its molecular mechanisms based on network pharmacology, molecular biological techniques and animal experiments. The underlying processes of plumbagin were investigated using gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: Plumbagin reduced the growth of DTC cells and increased the cells' apoptotic rate in vitro. Tumor volumes were significantly lessened after administration of plumbagin (P<0.05) as compared to tumor dimensions in the control group. In total, 1,225 cancer target genes and 89 putative plumbagin target genes were distinguished. As revealed in bioinformatics data, 12 predominant targets of plumbagin for treating DTC were obtained, and western blotting further confirmed that TP53, AKT1, CASP3, and PTEN were the most important biomolecules in the effects exerted by plumbagin. Conclusion: These findings show that plumbagin induced DTC cell apoptosis and suppressed tumor growth via TP53, AKT1, CASP3, and PTEN mediated pathways in human DTC cells. GO and KEGG enrichment analysis of differentially expressed genes (DEGs) related to plumbagin activation indicated pathways involved in cell survival, apoptosis, and metabolism, that were all significantly enriched.