Liang Cheng1, Tao Qin1, Jiguang Ma2, Wanxing Duan1, Qinhong Xu1, Xuqi Li3, Liang Han1, Wei Li1, Zheng Wang1, Dong Zhang1, Qingyong Ma1, Jianjun Lei1.
Abstract
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.
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.
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.
CONCLUSION: The accumulation of HIF-1α induced by hyperglycemia increases LDHA activity and HK2, PFKP expression, thereby promoting pancreatic glycolysis to facilitate cancer progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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.
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.
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.
CONCLUSION: The accumulation of HIF-1α induced by hyperglycemia increases LDHA activity and HK2, PFKP expression, thereby promoting pancreatic glycolysis to facilitate cancer progression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
Entities:
Keywords:
HIF-1α; Hyperglycemia; glycolysis; lactate dehydrogenase A; pancreatic cancer.
Year: 2019
PMID： 31241439 DOI： 10.2174/1871520619666190626120359
Source DB: PubMed Journal: Anticancer Agents Med Chem ISSN： 1871-5206 Impact factor: 2.505