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

J BUON. 2015 Jul-Aug;20(4):1107-14.

Abstract

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-α (TNF-α) is a pro-inflammatory cytokine implicated in the development and progression of cancer. The present study was designed to assess the impact of TNF-α 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-α inhibition using siRNA as inhibitory mechanism on SCC-4 cells. The study focused on the effect of TNF-α inhibition on apoptosis, autophagy and invasion in parallel with a panel of 20 genes involved in apoptosis and angiogenesis.

Results: TNF-α 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, NFκB, SEMA 3C, TNF-α, TGFB1, VEGFA, along with activation of PDGFB and SEMA 3D was observed. Our study confirms the important role of TNF-α and sustains that it might be a therapeutic target in OSCC.

Conclusions: TNF-α 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.

MeSH terms

  • Apoptosis
  • Autophagy
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Cell Line, Tumor
  • Epistasis, Genetic
  • Humans
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / therapy*
  • RNA Interference*
  • Transforming Growth Factor beta1 / physiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*

Substances

  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha