Interrogating ABCC1 and CASP1 as key players in epigallocatechin gallate’s action against radiotherapy-resistant nasopharyngeal carcinoma

Epigallocatechin gallate (EGCG), a well-characterized catechin in green tea, has demonstrated anti-tumor effects in nasopharyngeal carcinoma (NPC) cells and can enhance their sensitivity to radiotherapy. However, the pharmacological targets and mechanisms through which EGCG acts on radiotherapy-resistant NPC remain to be fully elucidated. RNA sequencing, network pharmacology, experimental validation, molecular docking, and molecular dynamics simulations were employed to uncover the molecular mechanisms by which EGCG mitigates radiotherapy resistance in NPC, with a focus on identifying potential therapeutic targets. Mining of online databases revealed 21 common targets between radiotherapy resistance in NPC and EGCG, from which a protein-protein interaction (PPI) network was constructed using STRING. Gene Ontology (GO) analysis identified biological processes relevant to the treatment of radiotherapy-resistant NPC by EGCG, such as response to xenobiotic stimulus, response to hypoxia, and key pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG), including pathogen infection, lipid metabolism, and cancer. Prognostic analysis led to the selection of two core genes (ABCC1, CASP1) for model construction. Notably, an elevated risk score was correlated with increased tumor malignancy and poorer prognosis. Significant differences in the immune microenvironment and immune checkpoints were observed between high- and low-risk groups. Experimental validation in HK1 cells confirmed the regulatory effect of EGCG on the expression of core targets. Molecular docking analysis revealed substantial interactions between EGCG and these targets, with simulation studies further substantiating stable binding. These findings provide a theoretical framework for the molecular mechanisms by which EGCG counteracts radiotherapy resistance in NPC. The identified core targets (ABCC1, CASP1) may serve as critical references for drug development and functional additive research associated with EGCG.