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To Explore the Inhibitory Mechanism of Quercetin in Thyroid Papillary Carcinoma through Network Pharmacology and
Ying Sun1,2, Wenjun Xie1,3, Ning Kang1
1Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China.
Abstract:
Quercetin, a flavonoid with anti-inflammatory and anticancer properties, is expected to be an innovative anticancer therapeutic agent for papillary thyroid carcinoma (PTC). However, the downstream signaling pathways that mediate quercetin-dependent anticancer properties remain to be deciphered. Herein, potential targets of quercetin were screened with several bioinformatic avenues including PharmMapper, Gene Expression Omnibus (GEO) database, protein-protein interaction (PPI) network, and molecular docking. Besides, western blot, CCK-8 transwell analysis of migration and invasion, flow cytometric analysis, and colony formation assays were performed to investigate the underlying mechanism. We found four core nodes (MMP9, JUN, SPP1, and HMOX1) by constructing a PPI network with 23 common targets. Through functional enrichment analysis, we confirmed that the above four target genes are enriched in the TNF, PI3K-AKT, and NF-κB signaling pathways, which are involved in the inflammatory microenvironment and inhibit the development and progression of tumors. Furthermore, molecular docking results demonstrated that quercetin shows strong binding efficiency with the proteins encoded by these 4 key proteins. Finally, quercetin displayed strong antitumor efficacy in PTC cell lines. In this research, we demonstrated the application of network pharmacology in evaluating the mechanisms of action and molecular targets of quercetin, which regulates a variety of proteins and signaling pathways in PTC. These data might explain the mechanism underlying the anticancer effects of quercetin in PTC.
Insights
Quercetin shows potential as an anticancer agent for papillary thyroid carcinoma (PTC). This study identified key molecular targets and signaling pathways, like TNF and PI3K-AKT, involved in quercetin
Area of Science:
- * Pharmacology
- * Molecular Biology
- * Bioinformatics
Background:
- * Quercetin, a flavonoid, exhibits anti-inflammatory and anticancer properties.
- * Its therapeutic potential for papillary thyroid carcinoma (PTC) is promising but requires mechanistic elucidation.
- * Downstream signaling pathways mediating quercetin's anticancer effects in PTC are not fully understood.
Purpose of the Study:
- * To investigate the molecular targets and signaling pathways of quercetin in papillary thyroid carcinoma (PTC).
- * To evaluate the anticancer efficacy of quercetin in PTC cell lines using network pharmacology.
- * To provide a mechanistic basis for quercetin's application in PTC treatment.
Main Methods:
- * Bioinformatic screening using PharmMapper and Gene Expression Omnibus (GEO) database.
- * Protein-protein interaction (PPI) network construction and analysis.
- * Molecular docking, western blot, CCK-8, transwell, flow cytometry, and colony formation assays.
Main Results:
- * Four core targets (MMP9, JUN, SPP1, HMOX1) were identified through PPI network analysis.
- * These targets are enriched in TNF, PI3K-AKT, and NF-κB signaling pathways, crucial for tumor development.
- * Molecular docking confirmed strong binding affinity between quercetin and the identified protein targets.
- * Quercetin demonstrated significant antitumor efficacy in PTC cell lines.
Conclusions:
- * Network pharmacology effectively identified quercetin's molecular targets and pathways in PTC.
- * Quercetin regulates multiple proteins and signaling pathways, inhibiting PTC progression.
- * These findings support quercetin as a potential therapeutic agent for papillary thyroid carcinoma.
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