HMOX1在低氧条件下对胶质瘤干细胞的作用  

Effect of HMOX1 on Glioma Stem Cells under Hypoxia

作　　者：宋佳伦 王心正[1] 吴瑾 李爱玲[1] 满江红[1] 

机构地区：[1]军事医学科学院生物医学分析中心,北京100850

出　　处：《科学技术与工程》2017年第31期193-198,共6页Science Technology and Engineering

基　　金：国家自然科学基金面上项目(81572889)资助

摘　　要：HMOX1(Heme Oxygenase 1)属于血红素加氧酶家族,作为血红素分解代谢中的必须酶,在恶性胶质瘤中高表达。脑胶质瘤干细胞(Glioma Stem Cell,GSC)是胶质瘤中的一小群肿瘤细胞,具有无限增殖、自我更新、多向分化的能力,被认为是肿瘤发生、复发、转移的根源。本实验通过质谱筛选,发现HMOX1特异性在胶质瘤干细胞中被低氧诱导高表达。目前关于HMOX1蛋白与缺氧环境下GSC的功能相关性未见文献报道。为了研究HMOX1是否在低氧时对GSC有调控作用,我们用慢病毒感染体系在GSC中敲低HMOX1表达,接着对细胞进行1%O_2低氧培养,用Western Blot检测基因干涉效果,用Tumor Sphere形成实验观察GSC细胞表型。实验结果表明,在低氧条件下干涉GSC中HMOX1基因的表达对GSC的生长及存活有明显的抑制。综上所述,HMOX1在GSC中特异性被低氧诱导高表达,且对GSC的生长存活具有调控作用,提示HMOX1有可能是GSC在低氧微环境中的重要调控因子。HMOX1( Heme Oxygenase 1) belongs to the family of heme oxygenase,which is the essential enzyme in heme catabolism and is highly expressed in malignant gliomas. Glioma stem cells( GSCs) are a small population of tumor cells,with the ability of unlimited proliferation,self-renewal and differentiation. GSCs are considered to be the causes of tumor initiation,recurrence and metastasis. In this study,we performed a mass spectrometry screen and found that HMOX1 was specifically induced in GSC under hypoxia. To our knowledge,there is no report on the function of HMOX1 in GSCs under hypoxic environment. To study whether HMOX1 was involved in GSCs regulation under hypoxia,we knocked down HMOX1 expression in GSC by using lentivirus system,and then cultured GSCs in 1% O_2 condition. The knock-down effect was examined by Western Blot and the cell phenotype was investigated by tumor sphere formation experiment. Our results showed that knocking down HMOX1 significantly inhibited GSC cell viability and tumor sphere formation. Altogether,our studies suggested that HMOX1 is preferentially induced in GSCs under hypoxia and plays critical roles in GSC maintenance under the hypoxic condition.

关 键 词：HMOX1 胶质瘤干细胞 低氧 TUMOR SPHERE 

分 类 号：Q28[生物学—细胞生物学]