Expression and significance of hypoxia-inducible factor-1α and MDR1/P-glycoprotein in laryngeal carcinoma tissue and hypoxic Hep-2 cells.
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 ofMDR1gene 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. TheHIF-1αandMDR1gene 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 theMDR1gene 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 ofMDR1gene expression induced by hypoxia in Hep-2 cells.
Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai 200080;
Jin
J
Xie
DA-Wei
DW
Li
Xin-Wei
XW
Chen
Fei
F
Wang
Pin
P
Dong
hypoxia; hypoxia inducible factor-1α; laryngeal neoplasms; multidrug resistance; p-glycoprotein