Corilagin increases the sensitivity of neuroblastoma to cisplatin by regulating the PI3K/AKT signaling pathway

Drug resistance remains the leading cause of cisplatin treatment failure in neuroblastoma (NB). This study aimed to investigate the potential of corilagin as an adjuvant therapy for overcoming cisplatin resistance in NB. In vitro functional assays—including cell viability (CCK-8), colony formation, transwell migration, and invasion assays—were conducted to evaluate the effects of corilagin in combination with cisplatin on human NB cell lines (SH-SY5Y and SK-N-BE(2)) and a cisplatin-resistant subline (SH-SY5Y/R). In vivo tumorigenesis experiments were performed to assess the suppressive effects of the corilagin-cisplatin combination on tumor growth initiated by SH-SY5Y and SH-SY5Y/R cells in mouse models. RNA sequencing was utilized to identify molecular mechanisms associated with cisplatin resistance and the therapeutic action of corilagin, followed by functional validation using 740Y-P, a specific agonist of the PI3K/AKT pathway. Our results showed that the combination of corilagin and cisplatin significantly inhibited proliferation, migration, invasion, and autophagic activity in SH-SY5Y/R cells, while robustly inducing apoptosis. Importantly, the PI3K/AKT signaling pathway was found to be hyperactivated during the development of cisplatin resistance, whereas corilagin effectively suppressed this activation. These findings indicate that corilagin enhances cisplatin sensitivity in NB cells through modulation of the PI3K/AKT signaling pathway.