the effect of hif 1α on glucose metabolism growth and apoptosis of pancreatic cancerous cells

• DOI: 10.6133/apjcn.2014.23.1.14
• Publication Date: 2014-03-01
• Authors: Yi Jiang; Bo Zhang; Guohao Wu; Guodong He
• Keywords: L-Lactate Dehydrogenase; Pyruvate Kinase; Gene Expression; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Apoptosis; Citrate (si)-Synthase; Protein Serine-Threonine Kinases; Hypoxia-Inducible Factor 1, alpha Subunit; Transfection; Cell Hypoxia; Isoenzymes; Pancreatic Neoplasms; Glucose; Cell Line, Tumor; Gene Knockdown Techniques; Humans; RNA Interference; Lactate Dehydrogenase 5; RNA, Small Interfering; Cell Proliferation

The aim of this study is to explore the possible role of HIF-1α in glucose metabolism, proliferation and apoptosis of pancreatic cancerous cells.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.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.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.