Zhou Xiaokang, Huang Danqing, Xue Zhongxiu, Xu Xiuhui, Wang Kai, Sun Yao, Kang Feiwu
Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Middle Yanchang Road 399, Shanghai 200072, P.R. China.
Int J Oncol. 2015;46(6):2346-54. doi: 10.3892/ijo.2015.2934. Epub 2015 Mar 26.
Hypoxia-inducible factor-1α (HIF-1α) is a key regulator for tumor cells and tissues to adapt to hypoxic condition. Suppressing the expression of HIF-1α is important to evaluate its effect on cancer cells. This study was carried out to analyze the effect of HIF-1α on the biological activation of human tongue squamous cell carcinoma (TSCC) SCC-15 cells. In this experiment, deferoxamine mesylate (DFO) was used to induce hypoxic condition. HIF-1α gene was suppressed by lentiviral vector. The effect of the level of HIF-1α expression was tested on the proliferation, cell cycle, cell apoptosis and cell invasion of SCC-15 cells. We demonstrated that SCC-15 cells showed a more aggressive phenotype after treated with DFO. Additionally, DFO was able to induce the expression of HIF-1α protein. Lentiviral vector can effectively inhibit HIF-1α expression on mRNA and protein level. Under normoxic or hypoxic conditions, downregulation of HIF-1α for SCC-15 cells induced cell apoptosis and inhibited growth and invasion. These results showed that suppressing the expression of HIF-1α inhibited the aggressive potential of SCC-15 cells under normoxic and hypoxic condition. Thus, finding an effective and safe pathway to inhibit the expression of HIF-1α can help us to improve the survival rate of human TSCC patients.
缺氧诱导因子-1α(HIF-1α)是肿瘤细胞和组织适应缺氧状态的关键调节因子。抑制HIF-1α的表达对于评估其对癌细胞的作用至关重要。本研究旨在分析HIF-1α对人舌鳞状细胞癌(TSCC)SCC-15细胞生物学活性的影响。在本实验中,使用甲磺酸去铁胺(DFO)诱导缺氧状态。通过慢病毒载体抑制HIF-1α基因。检测HIF-1α表达水平对SCC-15细胞增殖、细胞周期、细胞凋亡和细胞侵袭的影响。我们证明,DFO处理后SCC-15细胞表现出更具侵袭性的表型。此外,DFO能够诱导HIF-1α蛋白的表达。慢病毒载体能够在mRNA和蛋白质水平有效抑制HIF-1α的表达。在常氧或缺氧条件下,SCC-15细胞中HIF-1α的下调诱导细胞凋亡并抑制生长和侵袭。这些结果表明,抑制HIF-1α的表达可在常氧和缺氧条件下抑制SCC-15细胞的侵袭潜能。因此,找到一种有效且安全的途径来抑制HIF-1α的表达有助于提高人类TSCC患者的生存率。