title: Wortmannin influences hypoxia-inducible factor-1 alpha expression and glycolysis in esophageal carcinoma cells.
abstract: OBJECTIVE
  To investigate the influence of phosphatidylinositol-3-kinase protein kinase B (PI3K/AKT)-HIF-1α signaling pathway on glycolysis in esophageal carcinoma cells under hypoxia.
  
  
  METHODS
  Esophageal carcinoma cell lines Eca109 and TE13 were cultured under hypoxia environment, and the protein, mRNA and activity levels of hypoxia inducible factor-1 alpha (HIF-1α), glucose transporter 1, hexokinase-II, phosphofructokinase 2 and lactate dehydrogenase-A were determined. Supernatant lactic acid concentrations were also detected. The PI3K/AKT signaling pathway was then inhibited with wortmannin, and the effects of hypoxia on the expression or activities of HIF-1α, associated glycolytic enzymes and lactic acid concentrations were observed. Esophageal carcinoma cells were then transfected with interference plasmid with HIF-1α-targeting siRNA to assess impact of the high expression of HIF-1α on glycolysis.
  
  
  RESULTS
  HIF-1α is highly expressed in the esophageal carcinoma cell lines tested, and with decreasing levels of oxygen, the expression of HIF-1α and the associated glycolytic enzymes and the extracellular lactic acid concentration were enhanced in the esophageal carcinoma cell lines Eca109 and TE13. In both normoxia and hypoxic conditions, the level of glycolytic enzymes and the secretion of lactic acid were both reduced by wortmannin. The expression and activities of glycolytic enzymes and the lactic acid concentration in cells were reduced by inhibiting HIF-1α, especially the decreasing level of glycolysis was significant under hypoxic conditions.
  
  
  CONCLUSIONS
  The PI3K/AKT pathway and HIF-1α are both involved in the process of glycolysis in esophageal cancer cells.
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Hai-Yun
authors.initials: HY
authors.lastname: Zhou
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Tang
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Gui-Jun
authors.initials: GJ
authors.lastname: He
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hao
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Ya-Dong
authors.initials: YD
authors.lastname: Feng
authors.affiliation: Ling Zeng, Hai-Yun Zhou, Na-Na Tang, Wei-Feng Zhang, Gui-Jun He, Bo Hao, Ya-Dong Feng, Hong Zhu, Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D002277:Carcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D000072258:Tumor Hypoxia; D059016:Tumor Microenvironment; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019344:Lactic Acid; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin
keywords: Cell metabolism; Esophageal neoplasms; Glycolysis; Hypoxia; Hypoxia-inducible factor-1 alpha