Expression and significance of hypoxia-inducible factor-1 alpha and MDR1/P-glycoprotein in laryngeal carcinoma tissue and hypoxic Hep-2 cells

摘要

The present study aimed to evaluate the expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and MDR1/P-glycoprotein (P-gp) in human laryngeal squamous cell carcinoma (LSCC) tissues, and also to investigate the regulation of MDRI gene expression by HIF-la in Hep-2 cells under hypoxic conditions. The expression of HIF-1 alpha and MDR1/P-gp in human LSCC tissues was examined using immunohistochemistry. The HIF-1 alpha and MDRI gene expression in the Hep-2 cells was detected using real-time quantitative reverse transcription (QRT)-PCR and western blot analysis under normoxic and hypoxic conditions. In hypoxia, HIF-1 alpha expression was inhibited by RNA interference. HIF-1 alpha and MDR1/P-gp expression was high in the LSCC tissues and was associated with the clinical stage and lymph node metastasis (P<0.05). HIF-1 alpha expression was positively correlated with MDR1/P-gp expression (P<0.01). In the Hep-2 cells, HIF-1 alpha and MDR1/P-gp expression significantly increased in response to hypoxia. The inhibition of HIF-1 alpha expression synergistically downregulated the expression of the MDR1 gene in hypoxic Hep-2 cells. HIF-1 alpha expression is positively correlated with MDR1/P-gp expression in LSCC, and the two proteins may be able to serve as potential biomarkers for predicting the malignant progression and metastasis of LSCC. HIF-1 alpha may be critical for the upregulation of MDRI gene expression induced by hypoxia in Hep-2 cells.