低氧激活HIF-1α诱导舌鳞癌细胞上皮-间质转化

doi:10.19438/j.cjoms.2017.02.008

中国口腔颌面外科杂志 ›› 2017, Vol. 15 ›› Issue (2): 136-141.doi: 10.19438/j.cjoms.2017.02.008

低氧激活HIF-1α诱导舌鳞癌细胞上皮-间质转化

吴泽键¹, 周斌², 陈伟生¹, 吴晓平¹, 黄志权²

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

收稿日期:2016-06-27 出版日期:2017-03-20 发布日期:2017-04-13
通讯作者: 黄志权,E-mail：zhiquanhuang1978@126.com
作者简介:吴泽键（1982-）,男,学士,主治医师, E-mail：350455497@qq.com

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

WU Ze-jian¹, ZHOU Bin², CHEN Wei-sheng¹, WU Xiao-ping¹, HUANG Zhi-quan²

1.Department of Stomatology, People's Hospital of Puning City. Puning 515300;
2.Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital Affiliated to Sun Yat-sen University. Guangzhou 510120, Guangdong Province, China

Received:2016-06-27 Online:2017-03-20 Published:2017-04-13
Contact: 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/Abstract

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% O₂）或低氧（1% O₂）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mRNA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。

关键词: 低氧, 舌鳞状细胞癌, 上皮-间质转化, 低氧诱导因子1α

Abstract: 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.

Key words: Hypoxia, Tongue squamous cell carcinoma, Epithelial-to-mesenchymal transition, HIF-1α

中图分类号:

R739.8

吴泽键, 周斌, 陈伟生, 吴晓平, 黄志权. 低氧激活HIF-1α诱导舌鳞癌细胞上皮-间质转化[J]. 中国口腔颌面外科杂志, 2017, 15(2): 136-141.

WU Ze-jian, ZHOU Bin, CHEN Wei-sheng, WU Xiao-ping, HUANG Zhi-quan. Hypoxia induces epithelial-to-mesenchymal transition in human tongue squamous cell carcinoma via hypoxia inducible factor-1α[J]. China J Oral Maxillofac Surg, 2017, 15(2): 136-141.

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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

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