Elucidating EGCG’ s targets in nasopharyngeal carcinoma through combined cell-based assays and transcriptomic sequencing
摘要
Epigallocatechin gallate (EGCG) is a catechin, a type of flavonoid that is found in high concentrations in green tea. EGCG has been demonstrated to exhibit anti-proliferative, anti-angiogenic, and pro-apoptotic effects across various cancer cell lines. Furthermore, research indicates that EGCG plays a significant role in the antiproliferation and apoptosis of human nasopharyngeal carcinoma (NPC) cells. The anticancer activity of EGCG is mediated through its interference with multiple hallmarks of cancer; however, the specific targets and mechanisms by which EGCG combats NPC remain unclear.
MethodsThis study integrated cell line experiments, network pharmacology, molecular docking, and dynamics simulations to elucidate EGCG’s therapeutic mechanisms in NPC and identify potential targets, while scRNA-seq and MR analyses assessed key target gene-NPC relationships.
ResultsAnalysis of the GEO database and RNA sequencing of EGCG-treated NPC (HK-1) cells identified 165 potential targets associated with both EGCG and NPC. Network analysis revealed ten core targets, with EIF2AK2, IFIT1, and STAT1 being key. KEGG and GO analyses highlighted important pathways, including PI3K-Akt, phospholipase D signaling, and EBV infection. Molecular docking showed strong interactions between EGCG and the core targets, and molecular dynamics simulations confirmed complex stability. Finally, differential expression profiling of key target genes at the single-cell level demonstrated a concordance with transcriptomic data, while MR analyses validated the causal relationships between these target genes and the risk of NPC.
ConclusionThese findings offer a theoretical basis for the molecular mechanisms underlying EGCG’s therapeutic effects on NPC.