Reversal of sorafenib resistance in hepatocellular carcinoma by curcumol: insights from network pharmacology, molecular docking, and experimental validation

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 2, 2025

Background Curcumol, a bioactive sesquiterpenoid extracted from traditional Chinese medicine (TCM), has demonstrated potential in overcoming tumor drug resistance. However, its mechanisms reversing resistance, particularly hepatocellular carcinoma (HCC) resistant to sorafenib, are not yet fully elucidated. This study aims explore the molecular by which curcumol reverses sorafenib resistance HCC using combination of network pharmacology, docking, and vivo vitro experiments. Methods We identified targets genes associated with sorafenib-resistant HCC, resulting set overlapping targets. These intersection underwent enrichment analysis DAVID, protein-protein interaction (PPI) was constructed via STRING database Cytoscape. Molecular docking confirmed binding core In assays, including CCK-8, colony formation assay, apoptosis detection, wound healing, Transwell evaluated curcumol’s effects on cells. Western blotting assessed impact PI3K/AKT JAK/STAT3 signaling pathways. Additionally, xenograft mouse model established observe efficacy combined sorafenib. Results 117 for HCC. Among them, five targets—ALB, STAT3, HSP90AA1, HSP90AB1, SRC—showed strong affinity curcumol. KEGG pathway intersecting highlighted significant involvement PI3K/AKT, JAK/STAT3, Ras, Rap1, HIF-1, FoxO, mTOR experiments revealed that significantly enhanced sensitivity cells inhibiting cell proliferation, invasion, migration while promoting apoptosis. studies further effectively inhibited growth models. Conclusion provides compelling evidence can reverse modulating multiple pathways, Our findings suggest holds promise as novel therapeutic agent offering new avenue clinical intervention.

Language: Английский

Huaier enhances the antitumor effects of CDK 4/6 inhibitor by remodeling the immune microenvironment and gut microbiota in breast cancer

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119723 - 119723

Published: April 1, 2025

Language: Английский

Bridging Psychoneuroimmunology (PNI) and Cancer: New Insights and Innovations from China

Brain Behavior and Immunity Integrative, Journal Year: 2025, Volume and Issue: unknown, P. 100125 - 100125

Published: April 1, 2025

Language: Английский