ArticleFrontiers in pharmacology2026
Berberine and celecoxib synergistically suppress non-small cell lung cancer with EGFR/AKT/COX-2-related signaling: network pharmacology, molecular docking and experimental validation.
Article in Frontiers in pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality, and safer combination strategies with improved antitumor efficacy are still needed. Berberine (BBR), a natural isoquinoline alkaloid with multi-target pharmacological activity, and celecoxib (CXB), a selective cyclooxygenase-2 (COX-2) inhibitor, have shown antitumor potential. However, their combined efficacy and underlying mechanisms in NSCLC remain unclear. Methods: Network pharmacology, molecular docking, Chou-Talalay combination index analysis, complementary synergy analysis using SynergyFinder+, Results: Network analysis identified EGFR, AKT1, and PTGS2 (encoding COX-2) as candidate nodes, and molecular docking suggested predicted binding of BBR and CXB with EGFR, AKT1, and COX-2. Native-ligand re-docking showed acceptable reproduction of the crystallographic ligand poses. BBR and CXB synergistically reduced A549 and PC9 cell viability, with ZIP, HSA, Loewe, and Bliss analyses further supporting the multidose synergy, and a representative working combination dose was used for validation. The combination significantly inhibited proliferation, colony formation, migration, and invasion while promoting apoptosis. These effects were accompanied by suppression of EGFR and AKT phosphorylation, reduced COX-2 expression, downregulation of TNF-α, IL-1β, and CXCL8, decreased the Bcl-2/Bax ratio, and increased cleaved-Caspase-3. Conclusion: BBR combined with CXB exhibits synergistic antitumor activity in NSCLC cells and enhanced antitumor efficacy
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