Laryngeal squamous cell carcinoma progression is associated with the NFκB signaling pathway regulated by IκB kinase β

OBJECTIVE: We aimed to analyze the association of NFκB signaling pathway with the carcinogenesis of laryngeal squamous cell carcinoma (LSCC).

PATIENTS AND METHODS: Protein array was used to identify the differentially expressed proteins involved in NFκB signaling pathway between LSCC cells and normal throat mucosa. Correlation analysis between significantly expressed proteins and clinical characteristics (differentiation, clinical stage, and node metastasis) was performed. The expression of IκB kinase-β (IKK-β) in Hep-2 cells transfected with IKK-β-siRNA or pcDNA3.1-IKK-β was detected both by real-time polymerase chain reaction and western blot. Besides, a tetrazolium-based colorimetric assay (MTT), flow cytometer, and transwell assay were used to examine the proliferation, apoptosis, and migration rate of Hep-2 cells, respectively.

RESULTS: Three differentially expressed proteins were identified. Among them, tumor necrosis factor receptor 1 (TNFR1) and IKK-β were significantly up-regulated (p < 0.01) and Fas-associated via death domain (FADD) was significantly down-regulated (p < 0.01). The correlation analysis showed that IKK-β expression had a significant association with differentiation, clinical stage, and node metastasis (p < 0.05). Besides, high expressed IKK-β resulted in significantly increased proliferation and migration rate (p < 0.05). Reversely, Hep-2 cells transfected with IKK-β-siRNA showed significantly lower proliferation and migration rate (p < 0.05) and significantly higher apoptosis rate (p < 0.05) than normal cells.

CONCLUSIONS: The NFκB signaling pathway involved TNFR1, IKK-β, and FADD is significantly associated with the development of LSCC. Over-expressed IKK-β efficiently inhibits cell apoptosis and has positive effects on cell proliferation and migration.

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