<P>Background: Recent studies have suggested that 85% of pancreatic cancer patients accompanied
with impaired glucose tolerance or even Diabetes Mellitus (DM) and the invasive and migratory abilities of
pancreatic cancer could be enhanced by high glucose. This study aimed to investigate whether Hypoxia-
Inducible Factor-1α (HIF-1α) mediates hyperglycemia-induced pancreatic cancer glycolysis.
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Methods: The cellular glycolytic activity was assessed by determining lactate production, glucose uptake and
lactate dehydrogenase enzymatic activity. Pancreatic cancer cells (BxPC-3 cells) were transfected with short
hairpin RNA targeting the HIF-1α.
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Results: Hyperglycemia promotes pancreatic cancer glycolysis. Lactate dehydrogenase A (LDHA) activity and
hexokinase 2 (HK2), platelet-type of phosphofructokinase (PFKP) expression were significantly upregulated
under hyperglycemic conditions. HIF-1α knockdown prominently down-regulated the activity of LDHA and
the expression of HK2, PFKP and decreased lactate production in BxPC-3 cells. Under hypoxia condition,
hyperglycemia induced pancreatic glycolysis by mechanisms that are both dependent on HIF-1α and independent
of it.
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Conclusion: The accumulation of HIF-1α induced by hyperglycemia increases LDHA activity and HK2, PFKP
expression, thereby promoting pancreatic glycolysis to facilitate cancer progression.</P>