缺氧微环境下HIF-1α对胰腺癌细胞上皮间质转化及侵袭迁移的影响

Effect of HIF-1α on the epithelial mesenchymal transition and invasion and migration of pancreatic cancer cells under hypoxic condition

目的:探讨缺氧微环境下缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)对胰腺癌细胞上皮间质转化(epithelial-mesenchymal transition,EMT)及侵袭迁移的影响。方法:首先比较缺氧和常氧培养的胰腺癌细胞形态和体外侵袭迁移能力,以及HIF-1α和EMT相关因子的表达水平。然后通过HIF-1α抑制剂YC-1和siRNA基因沉默分别从蛋白和mRNA水平抑制HIF-1α的表达,检测缺氧培养的胰腺癌细胞体外侵袭迁移能力,以及EMT相关基因的表达水平。结果:形态学和分子水平证实缺氧诱导人胰腺癌细胞株AsP C-1、Capan-2、Panc-1的EMT改变,增强其体外侵袭和迁移能力。缺氧上调HIF-1α、Snail、N-cadherin的表达,下调E-cadherin的表达。抑制HIF-1α的表达后,Snail和N-cadherin表达下调,E-cadherin表达上调,并且体外侵袭迁移能力降低。结论:HIF-1α介导EMT在缺氧促进胰腺癌细胞侵袭迁移中发挥重要作用。

Objective: To investigate the effect of inducible factor- 1α( HIF- 1α) on epithelial- mesenchymal transition( EMT) and invasion and migration of pancreatic cancer cells under hypoxic condition. Methods: The morphology and migration and invision of pancreatic cancer cells and the expression levels of HIF- 1α and EMT related factors were compared under hypoxia and normoxia condition. HIF- 1α levels were inhibited by YC- 1 and siRNA,invasion and migration of pancreatic cancer cells,and the expression level of EMT related gene was detected. Results:As PC- 1,Panc- 1 and Capan- 2 were demonstrated to enhance their invasion and migration ability under hypoxia condition. Hypoxia up- regulated the expression of HIF- 1α,Snail,N- cadherin,down regulated E- cadherin. Inhibited the expression of HIF- 1α,Snail and N- cadherin expression decreased while E- cadherin expression increased,and down- regulated invasion and migration ability. Conclusion: HIF- 1α mediated EMT plays an important role in the invasion and migration of pancreatic cancer cells under hypoxia condition.