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<p>Gastric cancer (GC) is one of the main causes of cancer-related global mortality. The emergence of drug resistance and toxicity in current therapies highlights the need for novel treatment strategies. Quercetin, a natural flavonoid, has demonstrated anticancer activity; however, its molecular mechanism, particularly its effect on key targets in GC, remains underexplored. A comprehensive in silico and in vitro methods were used to elucidate the anticancer potential of Quercetin. Network pharmacology analysis was used to identify potential GC-related targets, followed by molecular docking and 200 ns molecular dynamics (MD) simulations to evaluate the binding affinity and stability of the Quercetin-target complex. In vitro experiments, including gene expression analysis and fluorescence binding assays, were conducted using AGS gastric cancer cells to validate the computational findings.nsulin-like growth factor 1 (IGF1) emerged as a key hub gene associated with GC progression. Molecular docking predicted a favorable interaction between Quercetin and IGF1, with a docking score of − 6.3 kcal/mol and multiple hydrogen-bond interactions. MD simulations confirmed the stability of the Quercetin-IGF1 complex, with reduced RMSD values (0.48 nm vs. 0.63 nm for unbound IGF1), favorable free energy profiles, and stable hydrogen bonding. In vitro studies demonstrated a significant downregulation of IGF1 mRNA expression (<i>p</i> &lt; 0.001) and a dose-dependent inhibition of IGF1 activity by Quercetin. The integration of network pharmacology, computational modeling, and experimental validation suggests that Quercetin may modulate the IGF1 signaling axis and influence IGF1-associated pathways in gastric cancer. The stable binding and significant inhibitory effect observed suggests that Quercetin may interrupt IGF1-mediated signaling pathways involved in tumor growth and survival. This study identifies Quercetin as a potential modulator of IGF1-associated signaling pathways with significant therapeutic promise for gastric cancer. The findings provide mechanistic insights supporting the further development of Quercetin as a targeted therapy for IGF1-driven malignancies.</p>

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Quercetin targets IGF1 signaling in gastric cancer: a synergy of network pharmacology, molecular simulations, and in vitro functional assays

  • 期刊论文

  • 发表日期：

    2026年6月15日

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  • Shao-Ji Li,
  • Xiaoping Yang,
  • Wedad Mawkili,
  • Faten F. Bin Dayel,
  • Abduallah Mawkili,
  • Amirah Albaqami

摘要

Gastric cancer (GC) is one of the main causes of cancer-related global mortality. The emergence of drug resistance and toxicity in current therapies highlights the need for novel treatment strategies. Quercetin, a natural flavonoid, has demonstrated anticancer activity; however, its molecular mechanism, particularly its effect on key targets in GC, remains underexplored. A comprehensive in silico and in vitro methods were used to elucidate the anticancer potential of Quercetin. Network pharmacology analysis was used to identify potential GC-related targets, followed by molecular docking and 200 ns molecular dynamics (MD) simulations to evaluate the binding affinity and stability of the Quercetin-target complex. In vitro experiments, including gene expression analysis and fluorescence binding assays, were conducted using AGS gastric cancer cells to validate the computational findings.nsulin-like growth factor 1 (IGF1) emerged as a key hub gene associated with GC progression. Molecular docking predicted a favorable interaction between Quercetin and IGF1, with a docking score of − 6.3 kcal/mol and multiple hydrogen-bond interactions. MD simulations confirmed the stability of the Quercetin-IGF1 complex, with reduced RMSD values (0.48 nm vs. 0.63 nm for unbound IGF1), favorable free energy profiles, and stable hydrogen bonding. In vitro studies demonstrated a significant downregulation of IGF1 mRNA expression (p < 0.001) and a dose-dependent inhibition of IGF1 activity by Quercetin. The integration of network pharmacology, computational modeling, and experimental validation suggests that Quercetin may modulate the IGF1 signaling axis and influence IGF1-associated pathways in gastric cancer. The stable binding and significant inhibitory effect observed suggests that Quercetin may interrupt IGF1-mediated signaling pathways involved in tumor growth and survival. This study identifies Quercetin as a potential modulator of IGF1-associated signaling pathways with significant therapeutic promise for gastric cancer. The findings provide mechanistic insights supporting the further development of Quercetin as a targeted therapy for IGF1-driven malignancies.