低氧通过上调乙酰辅酶A羧化酶1促进肺腺癌A549细胞迁移

Hypoxia promotes lung adenocarcinoma A549 cells migration by upregulating acetyl-CoA carboxylase 1

目的探讨低氧通过乙酰辅酶A羧化酶1(ACC1)促进人肺腺癌A549细胞迁移的机制。方法低氧(5%O2)处理肺腺癌A549细胞,应用Transwell迁移实验检测细胞迁移能力,Western blotting检测ACC1表达及上皮-间质转化(EMT)相关蛋白的表达水平。结果与常氧(对照组)相比,低氧处理促进了A549细胞的迁移(P<0.01),低氧处理后ACC1表达上调(P<0.01),同时波形蛋白(vimentin)表达增加(P<0.05),E-钙黏蛋白(Ecadherin)表达下降(P<0.01);敲除ACC1后与对照组相比,A549细胞的迁移能力减弱(P<0.05),vimentin表达下降(P<0.05),E-cadherin表达增加(P<0.01);敲除ACC1后A549细胞在常氧和5%O2条件下迁移数目及vimentin、E-cadherin表达变化无统计学意义(P>0.05);补充亚油酸(LA)恢复低氧对A549细胞的促迁移作用(P<0.05)。结论低氧通过上调ACC1的表达促进肺腺癌A549细胞迁移及EMT转化。

Objective To investigate the mechanism of hypoxia to promote human lung adenocarcinoma A549 cells migration through acetyl-CoA carboxylase 1(ACC1).Methods Lung adenocarcinoma A549 cells were treated with hypoxia(5%O2).Transwell migration assay was used to detect cell migration ability.Western blotting was used to detect ACC1 expression and epithelial-mesenchymal transition(EMT)related protein expression.Results Compared with the normoxia(control group),hypoxia treatment promoted the migration of A549 cells(P<0.01),ACC1 expression was upregulated after hypoxia treatment(P<0.01),and vimentin expression was detected to increase significantly(P<0.05),Ecadherin expression decreased(P<0.01);Compared with the control group,migration of A549 cells was inhibited(P<0.05),vimentin expression was down-regulated(P<0.05),and E-cadherin expression increased after knocking down ACC1(P<0.01).After ACC1 was knocked down,the differences between the numbers of migration of A549 cells under normoxia and 5%O2 conditions and the expressions of vimentin and E-cadherin were not statistically significant(P>0.05).After linoleic acid(LA)supplementation,the hypoxia-induced migration promotion of A549 cells was restored.Conclusion Hypoxia can promote the migration and EMT transformation of lung adenocarcinoma A549 cells by up-regulating the expression of ACC1.