Inhibition of tumor necrosis factor alpha using RNA interference in oral squamous cell carcinoma.

PURPOSE: Oral squamous cell carcinoma (OSCC) is a disease with increased prevalence and unfavorable prognosis calling for development of novel therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine implicated in the development and progression of cancer. The present study was designed to assess the impact of TNF-alpha specific inhibition using small interference RNA (siRNA) in SSC-4 cells, a representative model for OSCC. METHODS: The present study evaluated the effect of TNF-alpha inhibition using siRNA as inhibitory mechanism on SCC-4 cells. The study focused on the effect of TNF-alpha inhibition on apoptosis, autophagy and invasion in parallel with a panel of 20 genes involved in apoptosis and angiogenesis. RESULTS: TNF-alpha inhibition was related with reduction of cell viability, activation of apoptosis and autophagy in parallel with the inhibition of migration in SCC-4 cells. Evaluating the impact on gene expression levels, inhibition of FASL-FADD, NFkappaB, SEMA 3C, TNF-alpha, TGFB1, VEGFA, along with activation of PDGFB and SEMA 3D was observed. Our study confirms the important role of TNF-alpha and sustains that it might be a therapeutic target in OSCC. CONCLUSIONS: TNF-alpha is a key mediator of the immune system, with important role in OSCC tumorigenesis, and might be considered as a therapeutic target using siRNA technology, particularly for those risk cases having FASL/FADD overexpressed.