Flavonoid derivative FB-15 inhibits the progression of nasopharyngeal carcinoma by targeting the PI3K-Akt signaling pathway.

Nasopharyngeal carcinoma (NPC) is an aggressive malignancy with notable clinical challenges, necessitating the search for innovative therapeutic strategies. FB-15, a derivative incorporating flavonoid and benzimidazole structures, has demonstrated significant anti-tumor activity in prior research. However, its effects on NPC remain unexplored. In this research, we explored the anti-cancer potential of FB-15 in NPC and elucidated its molecular mechanisms. Our results, based on CCK-8 assays, colony formation assays, EdU staining, cell cycle analysis, wound healing and Transwell assays, as well as Western blotting, demonstrated that FB-15 markedly inhibited NPC cell proliferation, migration, and invasion, and induced G0/G1 phase cell cycle arrest. Transcriptome sequencing and KEGG pathway analysis suggested that FB-15 exerts its anti-cancer activities primarily by suppressing the PI3K-Akt signaling pathway, a conclusion reinforced by Western blot analysis showing reduced phosphorylation levels of PI3K and Akt proteins. Rescue experiments further confirmed the involvement of this pathway: the PI3K-Akt activator 740 Y-P partially reversed the inhibitory effects of FB-15 in 5-8F cells, whereas co-treatment with the PI3K-Akt inhibitor MK-2206 and FB-15 in HK1 cells did not produce additive effects compared to MK-2206 alone. These findings support the notion that FB-15 exerts its anti-tumor effects primarily through inhibition of the PI3K-Akt signaling axis. Animal studies demonstrated that FB-15 significantly suppressed the growth of subcutaneous NPC tumors in nude mice while maintaining stable body weight. Immunohistochemical analysis confirmed that FB-15 downregulated Ki67 and Vimentin expression while upregulating the epithelial marker E-cadherin, suggesting its role in inhibiting epithelial-mesenchymal transition. These results highlight FB-15 as a potential therapeutic agent for NPC, underscoring its potential clinical application as a monotherapy or in combination with existing treatments.