糖酵解
胰腺癌
内科学
内分泌学
乳酸脱氢酶A
乳酸脱氢酶
厌氧糖酵解
磷酸果糖激酶
己糖激酶
缺氧(环境)
下调和上调
缺氧诱导因子
癌细胞
磷酸果糖激酶1
化学
生物
癌症
癌症研究
新陈代谢
医学
酶
生物化学
氧气
有机化学
基因
作者
Liang Cheng,Tao Qin,Jiguang Ma,Wanxing Duan,Qinhong Xu,Xuqi Li,Liyuan Han,Wei Li,Zheng Wang,Dong H. Zhang,Qingyong Ma,Jianjun Lei
出处
期刊:Anti-cancer Agents in Medicinal Chemistry
[Bentham Science]
日期:2019-12-02
卷期号:19 (12): 1503-1512
被引量:21
标识
DOI:10.2174/1871520619666190626120359
摘要
<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. </P><P> 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. </P><P> 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. </P><P> 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>
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