Downregulation of hypoxia-inducible factor-1a inhibits growth, invasion, and angiogenesis of human salivary adenoid cystic carcinoma cells under hypoxia

Abstract

Surgical and medical treatments usually fail to completely remove the primary lesions of salivary adenoid cystic carcinoma (SACC), resulting in local recurrence due to its strong infiltration, hematogenous metastasis and other unique biological behaviors. Targeted gene therapy, including hypoxia-inducible factor-1a (HIF-1a) therapy, sheds new light on the treatment of salivary gland tumors. However, the mechanisms underlying the downregulation of HIF-1a expression in SACC have not been well studied. The present study aimed to determine the effects of HIF-1a downregulation on the proliferation, invasion, apoptosis, cell cycle and angiogenesis of hypoxic SACC-83 cells, and to elucidate the molecular mechanisms underlying these effects. Western blot analysis was used to evaluate the protein expression levels of HIF-1a and matrix metalloproteinase-2 (MMP-2). Angiogenesis and the protein expression of vascular endothelial growth factor (VEGF) were detected by tube formation assay of human umbilical vein endothelial cells and ELISA, respectively. It was revealed that short hairpin RNA was considerably downregulated following overexpression of HIF-1a. In addition, downregulation of HIF-1a inhibited the expression of VEGF and MMP-2, as well as the proliferation, invasion, migration, and tube formation of hypoxic SACC-83 cells, while inducing apoptosis in these cells. These results suggest that the downregulation of HIF-1a may be a novel targeted therapy for SACC.