摘要
背景与目的:钙黏附蛋白E(E-cadherin)低表达与癌细胞的高侵袭转移潜能密切相关,但其与癌细胞葡萄糖代谢的关系鲜见报道。该研究旨在探讨E-cadherin与胰腺癌PANC-1细胞糖酵解效应的关系。方法:通过转化生长因子β(transforming growth factorβ,TGF-β)引起E-cadherin低表达、敲减与E-cadherin相互作用的β-连环蛋白(β-catenin)的基因以及过表达E-cadherin等方法,检测PANC-1细胞通过糖酵解效应吸收葡萄糖和生成乳酸能力的变化以及糖酵解通路中关键基因的表达。结果:E-cadherin可以负向调控PANC-1细胞的糖酵解效应,抑制肿瘤细胞吸收葡萄糖和分泌乳酸的能力(P<0.05)。而与其相互作用的β-catenin可以正向调控PANC-1细胞的糖酵解效应,促进葡萄糖的吸收和乳酸的生成,结果差异有统计学意义(P<0.05)。同时糖酵解效应的关键调控分子去乙酰化酶3(sirtuin 3,SIRT3)也可以引起PANC-1细胞中E-cadherin表达的改变。结论:PANC-1细胞中E-cadherin低表达可以引起葡萄糖代谢模式的转化,促进PANC-1细胞的糖酵解效应,同时通过导入糖酵解效应的关键调控分子SIRT3也可以引起E-cadherin表达的改变。这些结果为研究胰腺癌侵袭转移过程中糖代谢模式的转化提供了重要线索,为通过改变糖酵解效应进而影响胰腺癌的侵袭转移潜能提供了干预模式。
Background and purpose：Lower expression of E-cadherin is associated with metastasis of cancer cells, however, the correlation between E-cadherin and glucose metabolism has seldom been reported. This article studied the correlation between E-cadherin and glycolysis effect in PANC-1 cells.Methods：Through treatment of transforming growth factor β （TGF-β） in PANC-1 cells to decrease E-cadherin expression, knock-down the gene of E-cadherin interaction protein β-catenin, and overexpressing of E-cadherin, the effects of E-cadherin on the glucose uptake and lactate production ability and on the expression of key glycolytic genes were assessed.Results：E-cadherin negatively regulated the glycolytic effect of PANC-1 cells by inhibiting glucose uptake and lactate production （P〈0.05）. Moreover, E-cadherin interacting partner β-catenin signiifcantly promoted glucose metabolism transformation in PANC-1 cells （P〈0.05）. Moreover, key glycolysis regulator sirtuin 3 （SIRT3） could lower E-cadherin expression.Conclusion：Lower expression of E-cadherin induced the transformation of glucose metabolism transformation in PANC-1 cells and manipulation of E-cadherin expression level could change the glycolysis effect. Moreover, through maneuver glycolysis process could inhibit high metastatic potential of pancreatic cancer cells.
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2015年第2期81-86,共6页
China Oncology
基金
国家自然科学基金(81372651)
