title: The effect of HIF-1α on glucose metabolism, growth and apoptosis of pancreatic cancerous cells.
abstract: OBJECTIVE
  The aim of this study is to explore the possible role of HIF-1α in glucose metabolism, proliferation and apoptosis of pancreatic cancerous cells.
  
  
  METHODS
  The pancreatic cancerous BxPC-3 cells were cultured in normoxia or hypoxia (3% O2), respectively. Cell proliferation was determined by MTT assay, apoptosis was determined by Annexin V/PI staining. Expression of Pyruvate dehydrogenase kinase (PDK1), Lactate dehydrogenase (LDHA), pyruvate kinase M2 (PKM2) and citrate synthase (CS) was determined by Western-blot and Realtime PCR.
  
  
  RESULTS
  Under hypoxia, the expression of HIF-1α and the lactate production were increased. The expression of glucose metabolic enzymes PDK1, LDHA, PKM2 was also increased compared with that under aerobic condition. Hypoxia treatment had little effect on expression of CS. Under hypoxia, knockdown of HIF-1α inhibited the production of lactate and the expression of PDK1, LDHA and PKM2. Knockdown of HIF-1α repressed the growth of pancreatic cancer BxPC-3 cells and induced apoptosis of the cells under hypoxia.
  
  
  CONCLUSIONS
  Under hypoxia, the expression of HIF-1α is induced, leading to the increase of glycolysis in BxPC-3 cells possibly through upregulation of the enzymes related to glycolysis. HIF-1α knockdown can inhibit the prolife ratio and promote apoptosis of pancreatic cancerous BxPC-3 cells in vitro.
authors.affiliation: Department of General Surgery, Institute of General Surgery, 180 Fenglin Road, Zhongshan Hospital, Fudan University, Shanghai 200032, China. wu.guohao@zs-hospital.sh.cn.
authors.forename: Guodong
authors.initials: G
authors.lastname: He
authors.forename: Yi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Guohao
authors.initials: G
authors.lastname: Wu
mesh_terms: D017209:Apoptosis; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002950:Citrate (si)-Synthase / Q000032:analysis / Q000235:genetics; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics; D007770:L-Lactate Dehydrogenase / Q000032:analysis / Q000235:genetics; D000080864:Lactate Dehydrogenase 5; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000235:genetics; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D011770:Pyruvate Kinase / Q000032:analysis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007527:Isoenzymes; C000631429:PDK1 protein, human; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034741:RNA, Small Interfering; D007770:L-Lactate Dehydrogenase; D000080864:Lactate Dehydrogenase 5; D002950:Citrate (si)-Synthase; D011770:Pyruvate Kinase; D017346:Protein Serine-Threonine Kinases; D005947:Glucose