Exploring Molecular Targets of Quercetin for the Treatment of Nicotine-Related Oral Carcinoma: A Network Pharmacology Analysis and In Vitro Study.

Nicotine, which is enriched in tobacco, has been identified as an important factor in the development of oral cancer. The natural flavonoid quercetin has potential anti-tumor properties due to its low toxicity and high efficacy. We aimed to explore the potential molecular targets of quercetin for the treatment of nicotine-related oral cancer by network pharmacological analysis and to evaluate its efficacy in vitro experiments. A total of 29 potential target genes were identified, which may be associated with epithelial-mesenchymal transition (EMT), the receptor tyrosine kinase (RTK) pathway, and immune cell infiltration, as well as acquired resistance to various chemotherapeutic agents. Molecular docking and molecular dynamics simulation indicated that quercetin may bind more strongly to potential key genes (THBS1, SERPINE1, and IGF1R). Quercetin was shown to affect key gene expressions in nicotine-related oral cancer cells and attenuate their malignant phenotype in vitro experiments. A series of novel targets for quercetin in the treatment of nicotine-related oral cancer were identified. These findings not only help understand the pathogenesis of oral cancer but also help explore its precancerous preventive measures, which are of great value for oral cancer prevention.