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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 & OBJECTIVE: The low expression of E-cadherin is closely related to the high invasion and metastasis potential of cancer cells, but its relationship with the glucose metabolism in cancer cells is seldom reported. The aim of this study was to investigate the relationship between E-cadherin and glycolytic effect in pancreatic cancer PANC-1 cells. METHODS: The expression of E-cadherin was down-regulated by transforming growth factor β (TGF-β), the β-catenin gene knocked down by interaction with E-cadherin and the expression of E-cadherin Method to detect changes in ability of PANC-1 cells to absorb glucose and produce lactic acid through glycolysis and the expression of key genes in the glycolysis pathway. Results: E-cadherin negatively regulated the glycolytic effect of PANC-1 cells and inhibited the ability of tumor cells to absorb glucose and lactate (P <0.05). The interaction of β-catenin with PANC-1 cells can positively regulate the glycolytic effect and promote the absorption of glucose and the production of lactate. The difference was statistically significant (P <0.05). Simultaneously, sirtuin 3 (SIRT3), a key regulator of glycolysis, can also induce the change of E-cadherin expression in PANC-1 cells. CONCLUSION: Low expression of E-cadherin in PANC-1 cells can induce the transformation of glucose metabolism model and promote the glycolytic effect of PANC-1 cells. Meanwhile, the expression of E-cadherin can also be induced by the introduction of SIRT3, a key regulator of glycolysis Change. These results provide important clues for the study of the transformation of glucose metabolism during the invasion and metastasis of pancreatic cancer, and provide an intervention model for altering the invasion and metastasis potential of pancreatic cancer through changing the glycolytic effect.