Study on the regulatory mechanism and experimental verification of Ardisia crenata for the treatment of head and neck squamous cell carcinoma

Abstract

Abstract Objective Head and neck squamous cell carcinoma (HNSCC) is one of the most common squamous epithelial malignancies. Ardisia crenatahas an effect in the inhibition of tumor cells by regulating the cell cycle and inducing cell apoptosis. This study aimed to investigate the potential mechanism of A. crenata anti-HNSCC based on network pharmacology, molecular docking and in vitro experiments. Methods The active compounds of A. crenata and HNSCC related targets were retrieved from SwissTargetPrediction, BATMAN-TCM, and SymMap v2 databases. The protein-protein interaction (PPI) network was constructed and the key targets were screened. GO and KEGG enrichment was conducted in DAVID. Survival analysis and core targets identification were conducted in TISIDB. The main active compounds of A. crenata were docked with the corresponding core targets by AutoDockTools and Autodock Vina. The regulatory effect of A. crenata on HNSCC was verified in FaDu cells. Results 163 common target genes were identified as candidate targets of A. crenata for the treatment of HNSCC, the top core targets are TP53, GAPDH, AKT1, STAT3, CCND1 and SRC. KEGG pathway enrichment analysis indicated that A. crenata exerted anti-HNSCC effects mainly through pathways in cancer, prostate cancer, neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway, p53 signaling pathway, EGFR tyrosine kinase inhibitor resistance and endocrine resistance. It’s also confirmed that A. crenatacould effectively inhibit the proliferation of FaDu cells, and down-regulate the expression of p-PI3K and p-AKT. Conclusion The study demonstrated the multi-targets and multi-pathways characteristics of A. crenata in the treatment of HNSCC.