Exploring the Therapeutic Potential of Oridonin in the Treatment of Laryngeal Cancer: A Comprehensive Strategy Involving Network Pharmacology, Molecular Docking, Dynamic Simulation, and Experimental Verification

Laryngeal Cancer (LC) is one of the most common malignant tumors of the head and neck, with high morbidity and mortality rates worldwide. Oridonin (Ori), a natural tetracyclic diterpenoid, exhibits notable anti-tumor properties. However, its efficacy and underlying mechanism in LC remain to be elucidated. This study employed comprehensive network pharmacology, molecular docking, and molecular dynamic simulation to investigate the molecular targets and mechanisms underlying the anti-LC effects of Ori, followed by in vitro validation of its key mechanisms. A total of 172 potential therapeutic targets of Ori for LC were identified. GO and KEGG analyses indicated that Ori's anti-LC mechanism primarily involved the PI3K-Akt, Ras, MAPK, and Rap1 signaling pathways. The PPI network and molecular docking analyses revealed that Akt1, EGFR, and MAPK1 are potential core targets of Ori. Additionally, molecular dynamics simulations and bioinformatics analyses further confirmed that these proteins are key candidate targets. In vitro, Ori inhibited the proliferation of LC Hep-2 and TU212 cells, induced Apoptosis, arrested the cell cycle at the G1 phase, and suppressed migration and invasion. WB assays further showed that Ori significantly downregulated p-AKT expression in the PI3K/Akt pathway. These findings indicate that Ori represents a promising therapeutic candidate for LC.

dynamics simulation; laryngeal cancer; molecular docking; network pharmacology; oridonin.