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Excess glucose induces hypoxia-inducible factor-1α in pancreatic cancer cells and stimulates glucose metabolism and cell migration
- Source :
- Cancer biologytherapy. 14(5)
- Publication Year :
- 2013
-
Abstract
- Pancreatic cancer patients frequently show hyperglycemia, but it is uncertain whether hyperglycemia stimulates pancreatic cancer cells. We have investigated whether excess glucose induces hypoxia-inducible factor-1α (HIF-1α) and stimulates glucose metabolism and cell migration in pancreatic cancer cells. We studied wild-type (wt) MiaPaCa2 pancreatic cancer cells and a MiaPaCa2 subline (namely si-MiaPaCa2) that had HIF-1α-specific small interfering RNA. Wt-MiaPaCa2 cells are known to be HIF-1α-positive in hypoxia and HIF-1α-negative in normoxia, whereas si-MiaPaCa2 cells are devoid of HIF-1α in both normoxia and hypoxia. We incubated these cells with different amounts of glucose and determined HIF-1α mRNA and protein by real-time polymerase chain reaction and western blotting. We determined glucose consumption, lactate production and intracellular hexokinase-II and ATP to assess glucose metabolisms and determined pyruvate dehydrogenase kinase-1, reactive oxygen species and fumarate to assess mitochondrial activities. Further, we studied cell migration using a Boyden chamber. Excess glucose (16.7−22.2mM) increased HIF-1α in hypoxic wt-MiaPaCa2 cells. HIF-1α expression increased ATP contents and inhibited mitochondrial activities. Extracellular glucose and hypoxia stimulated glucose metabolisms independent of HIF-1α. Excess glucose stimulated the migration of wt- and si-MiaPaCa2 cells in both normoxia and hypoxia. Thus, glucose stimulated cell migration independent of HIF-1α. Nevertheless, hypoxic wt-MiaPaCa2 cells showed greater migrating ability than their si-MiaPaCa2 counterparts. We conclude that (1) excess glucose increases HIF-1α and ATP in hypoxic wt-MiaPaCa2 cells, (2) extracellular glucose and hypoxia regulate glucose metabolisms independent of HIF-1α and (3) glucose stimulates cell migration by mechanisms that are both dependent on HIF-1α and independent of it.
- Subjects :
- Cancer Research
medicine.medical_specialty
Snf3
Cell Growth Processes
Biology
Carbohydrate metabolism
Protein Serine-Threonine Kinases
Adenosine Triphosphate
Cell Movement
Internal medicine
Cell Line, Tumor
medicine
Extracellular
Humans
Glycolysis
RNA, Messenger
RNA, Small Interfering
Pharmacology
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
Cell migration
Hypoxia (medical)
Hypoxia-Inducible Factor 1, alpha Subunit
Pancreatic Neoplasms
Endocrinology
Glucose
Oncology
Hypoxia-inducible factors
Hyperglycemia
Molecular Medicine
medicine.symptom
Reactive Oxygen Species
Intracellular
Research Paper
Subjects
Details
- ISSN :
- 15558576
- Volume :
- 14
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Cancer biologytherapy
- Accession number :
- edsair.doi.dedup.....458e5d952a0f919116a737cf9f62ea3e