低氧激活HIF-1α诱导舌鳞癌细胞上皮-间质转化  

Hypoxia induces epithelial-to-mesenchymal transition in human tongue squamous cell carcinoma via hypoxia inducible factor-1α

作　　者：吴泽键 周斌[2] 陈伟生 吴晓平 黄志权[2] 

机构地区：[1]普宁市人民医院口腔科,广东普宁515300 [2]中山大学附属孙逸仙纪念医院口腔颌面外科,广东广州510120

出　　处：《中国口腔颌面外科杂志》2017年第2期136-141,共6页China Journal of Oral and Maxillofacial Surgery

基　　金：广东省自然科学基金(2016A030313348);中央高校基本科研业务费专项资金(16ykjc17)

摘　　要：目的 :探讨低氧微环境诱导人舌鳞癌细胞上皮-间质转化以及HIF-1α在该过程中的作用。方法 :体外常氧(20%O_2)或低氧(1%O_2)状态下培养舌鳞癌SCC9、CAL27细胞48 h,Western免疫印迹和实时定量PCR检测上皮间质标记蛋白vimentin、fibronectin和E-cadherin的表达变化和HIF-1α的表达水平,Transwell小室检测细胞的迁移能力。通过小干扰RNA(HIF-1α-Si)转染舌鳞癌细胞,检测HIF-1α、vimentin、fibronectin与E-cadherin蛋白表达以及细胞迁移能力的变化。应用SPSS13.0软件包对数据进行独立样本t检验。结果:人舌鳞癌细胞SCC9、CAL27在低氧环境中培养48 h后,间质标志蛋白vimentin和fibronectin在蛋白和m RNA水平均显著升高,上皮标志蛋白E-cadherin表达降低,HIF-1α表达上调,细胞迁移能力显著增强。小干扰RNA(siRNA)转染舌鳞癌细胞SCC9、CAL27并于低氧下培养后,HIF-1α表达显著降低,vimentin和fibronectin表达也显著降低,E-cadherin表达升高,细胞迁移能力显著下降。结论:低氧通过上调HIF-1α表达而促进人舌鳞癌细胞发生上皮-间质转化及转移。PURPOSE ： To investigate the effect of hypoxia on epithelial-to-mesenchymal transition in human tongue squamous cell carcinoma （TSCC） and the role of HIF-1α in this process. METHODS ： TSCC cell lines SCC9 and CAL27 were cultured under hypoxia （1% O2） or normoxia （20% O2） for 48 h. Western blot and qRT-PCR were used to detect expression of vimentin, fibronectin, E-cadherin and HIF-1α at protein and mRNA level, respectively. Transwell assay was used to detect cell invasion. After transfected HIF-1α with siRNA, HIF-1α, vimentin, fibronectin and E-cadherin expression, as well as invasion, were furthered detected in SCC9 and CAL27 cells. SPSS 13.0 software package was used for statistical analysis. RESULTS ： Both SCC9 and CAL27 cells under hypoxia for 48 h showed upregulated vimentin and fibronectin, downregulated E-cadherin and upregulated HIF-1α expression, as well as increased invasion. After knocking down of HIF-1α with siRNA, HIF-1α, vimentin and fibronectin were significantly downregulated but E-cadherin was upregulated in SCC9 and CAL27 cells under hypoxia, with decreased invasion. CONCLUSION ： Hypoxia induces epithelial-to-mesenchymal transition and metastasis of TSCC via upregulating HIF-1α.

关 键 词：低氧 舌鳞状细胞癌 上皮-间质转化 低氧诱导因子1Α 

分 类 号：R739.86[医药卫生—肿瘤]