Inhibition of proliferation and metastasis of nasopharyngeal carcinoma by kaempferol via down-regulation of c-Jun.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a highly aggressive malignancy of the head and neck, characterized by poor therapeutic outcomes. Kaempferol (Kae) has demonstrated significant potential in curbing tumor proliferation and metastasis, but its precise mechanism in NPC remains unclear. Given the critical role of the c-Jun/vascular endothelial growth factor (VEGF) axis in tumor progression, this study aims to investigate whether Kae suppresses NPC growth and metastasis through inhibition of this signaling pathway. METHODS: Cell viability was assessed via Cell Counting Kit-8 (CCK-8) assay, while clonogenic potential was evaluated through colony formation assay. Apoptotic rates were analyzed by flow cytometry, and cell migratory and invasive capacities were assessed using wound healing and Transwell assays, respectively. The expression of c-Jun and VEGF at both mRNA and protein levels was analyzed through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting. Furthermore, a xenograft mouse model was established to evaluate the in vivo antitumor efficacy of Kae and its regulatory effect on c-Jun/VEGF protein expression. RESULTS: Kae exerted a pronounced inhibitory effect on NPC cell proliferation in a time- and dose-dependent manner. In addition, Kae notably induced apoptosis and markedly suppressed the migration and invasion of C666-1 cells. Mechanistically, Kae treatment led to a dose-dependent downregulation of c-Jun and VEGF expression at both transcript and protein levels. Moreover, silencing c-Jun partially reversed the Kae-induced growth inhibition, apoptosis, and suppression of migration and invasion. Consistently, in vivo experiments demonstrated that Kae significantly suppressed tumor volume without exerting adverse effects on body weight, increased tumor cell apoptosis, caused histopathological damage to tumor tissues, and downregulated c-Jun and VEGF protein expression. CONCLUSIONS: Kae effectively attenuates NPC cell proliferation, induces apoptosis, and reduces migration and invasion via suppression of the c-Jun/VEGF signaling axis.