Effects of hypoxia inducible factor-1alpha (HIF-1alpha) on the growth & adhesion in tongue squamous cell carcinoma cells

Ying Song, Wenxia Wang, Xun Qu, Shanzhen Sun
Indian Journal of Medical Research 2009, 129 (2): 154-63

BACKGROUND & OBJECTIVES: Hypoxia-inducible factor-1 alpha (HIF-1alpha) is a central transcriptional regulator of hypoxic response. Suppression of HIF-1alpha is important for exploring hypoxia-induced pathophysiological events. This study was carried out to analyze the hypoxia-induced changes of biological characteristics in the human tongue squamous cell carcinoma cell line Tca8113 and evaluate the effects of HIF-1alpha on the phenotype of the tongue squamous cell carcinoma.

METHODS: HIF-1alpha gene was silenced with synthesized short interfering ribonucleic acids (siRNA). HIF-1alpha expression was measured on mRNA level by real-time reverse transcription (RT)-PCR and protein level by Western blot and immunofluorescence. The cell cycle and apoptosis of Tca8113 cells were analyzed by FACS. The proliferation and adhesion of Tca8113 cells were determined by MTT colorimetric assay.

RESULTS: Tca8113 could survive and showed a more aggressive phenotype under hypoxic condition. Exposure to hypoxia induced a prolonged elevation of HIF-1alpha protein and transfection of siRNA targeting HIF-1alpha (siRNA(HIF-1alpha)) reduced HIF-1alpha synthesis as measured on mRNA and protein level. Under normoxic or hypoxic conditions, treatment of Tca8113 cells with siRNA(HIF-1alpha) induced cell apoptosis and inhibited the growth and adhesion.

INTERPRETATION & CONCLUSION: siRNA(HIF-1alpha) could attenuate the tolerance against hypoxia in Tca8113 cells and inhibit their aggressive potential. Interfering with HIF-1alpha pathways by siRNA strategy may provide a therapeutic target for human tongue squamous cell carcinomas.

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