Analysis of Hypoxia Inducible Factor-1α Expression and Its Effects on Glycolysis of Esophageal Carcinoma.

ABSTRACT

We investigated the regulatory effects of hypoxia-inducible factor-1a (HIF-1α) on glycolysis metabolism in esophageal carcinoma (ESCA) cells. A series of bioinformatics databases and tools were used to investigate the expression and role of HIF-1α in ESCA. The expression of HIF-1a in ESCA tissues and adjacent tissues was validated by real-time PCR. Small interfering RNA (siRNA) was used to inhibit HIF-1α-related genes in human ESCA cells (Eca109 and KYSE150). Cell proliferation was detected by the CCK-8 assay. The expression of HIF-1α and glycolytic enzymes were investigated by real-time PCR and Western blot. HIF-1α is highly expressed in ESCA and is involved in many biological processes such as cell hypoxia reaction, glucose metabolic process. Further in vitro experiments showed that expression of HIF-1α in Eca109 and KYSE150 significantly increased under hypoxia compared with normoxia conditions. Also, the glucose uptake and lactate production under hypoxia were higher. The expression levels of hexokinase 2 (HK2) and pyruvate dehydrogenase kinase 1 (PDK1), glycolysis-related genes, were significantly increased under hypoxia. After siRNA knockdown of HIF-1a in Eca109 and KYSE150, the glucose uptake and lactate production, as well as cell proliferation were significantly decreased under hypoxia, and HK2 and PDK1 were significantly downregulated. HIF-1α promotes glycolysis of ESCA cells by upregulating the expression of HK2 and PDK1 under hypoxia.