Uncovering celecoxib’s anti-breast cancer mechanisms through network pharmacology, molecular docking, and dynamics

Celecoxib has gained attention as a potential anti-tumor agent in breast cancer. This study systematically elucidated the therapeutic mechanisms of celecoxib in this malignancy. The candidate targets of celecoxib and the molecular targets associated with breast cancer were retrieved. The protein-protein interaction (PPI) networks were established. GO and KEGG pathway enrichment analyses were performed. Molecular docking simulations and normal mode analysis (NMA) were used. This study identified 104 candidate targets of celecoxib, 18,389 potential targets implicated in breast cancer, and 95 overlapping targets. GSK3B, CCND1, PTGS2, CDK2, CDK4, and MTOR were identified as key hub proteins in celecoxib’s anti-breast cancer activity. These overlapping candidates were associated with protein serine/threonine kinase activity and cyclin-dependent protein kinase regulator activity and involved in FoxO, prolactin, p53, and PI3K-Akt pathways. Celecoxib exhibited high binding affinity for GSK3B, CDK4, and MTOR, while showing moderate binding affinity for CDK2. Dynamic simulations revealed stable binding, minimal structural perturbations, and system-dependent rigidity profiles of the docked celecoxib-protein complexes. In vitro experimental results showed that celecoxib suppressed cell colony formation, migration, and invasion and enhanced apoptosis in MCF-7 cells by downregulating MTOR. This study suggests that celecoxib may exert anti-cancer effects in breast cancer via multiple targets (e.g., MTOR) and pathways.