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

Abstract

The present study aimed to evaluate the expression of hypoxia‑inducible factor‑1α (HIF‑1α) and MDR1/P‑glycoprotein (P‑gp) in human laryngeal squamous cell carcinoma (LSCC) tissues, and also to investigate the regulation of MDR1 gene expression by HIF‑1α in Hep‑2 cells under hypoxic conditions. The expression of HIF‑1α and MDR1/P‑gp in human LSCC tissues was examined using immunohistochemistry. The HIF‑1α and MDR1 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‑1α expression was inhibited by RNA interference. HIF‑1α 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‑1α expression was positively correlated with MDR1/P‑gp expression (P<0.01). In the Hep‑2 cells, HIF‑1α and MDR1/P‑gp expression significantly increased in response to hypoxia. The inhibition of HIF‑1α expression synergistically downregulated the expression of the MDR1 gene in hypoxic Hep‑2 cells. HIF‑1α 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‑1α may be critical for the upregulation of MDR1 gene expression induced by hypoxia in Hep‑2 cells.