中华放射医学与防护杂志
中華放射醫學與防護雜誌
중화방사의학여방호잡지
Chinese Journal of Radiological Medicine and Protection
2010年
2期
165-168
,共4页
童流妹%冯丽波%陆雪官%陈列松%郭信伟%田野
童流妹%馮麗波%陸雪官%陳列鬆%郭信偉%田野
동류매%풍려파%륙설관%진렬송%곽신위%전야
胶质瘤细胞%乏氧%肿瘤干细胞%HIF-1α%Notch 1
膠質瘤細胞%乏氧%腫瘤榦細胞%HIF-1α%Notch 1
효질류세포%핍양%종류간세포%HIF-1α%Notch 1
Glioma%Hypoxia%Cancer stem cell%HIF-1α%Notch 1
目的 探讨微环境乏氧是否能通过肿瘤干细胞途径引起脑胶质瘤放射敏感性的改变以及可能的相关机制.方法 选择脑胶质瘤SHG44和U251细胞株分别在常氧(20%0_2)、乏氧(1%0_2)12和24 h的条件下培养后,应用流式细胞仪检测CD133表达阳性细胞的比例,细胞克隆形成实验绘制细胞存活曲线以观察其放射敏感性,采用Western blotting方法测定基因HIF-la及其下游基因Notch 1蛋白的表达水平.结果 与常氧培养条件比,SHG44和U251细胞乏氧12和24 h后CD133阳性表达比例明显升高;SF_2(2 Gy照射时的存活分数)均升高.在乏氧12和24 h培养时,SHG44细胞株的氧增强比的值分别为1.54和1.38.而U251细胞株则分别为1.44和1.23,提示在乏氧培养时细胞的放射敏感性下降;与常氧培养条件比,乏氧时HIF-la和Notch 1的蛋白表达水平均明显升高.结论 微环境乏氧能通过提高肿瘤干细胞的比例而降低脑胶质瘤细胞的放射敏感性,其可能的作用信号途径为HIF-la-Notch 1.
目的 探討微環境乏氧是否能通過腫瘤榦細胞途徑引起腦膠質瘤放射敏感性的改變以及可能的相關機製.方法 選擇腦膠質瘤SHG44和U251細胞株分彆在常氧(20%0_2)、乏氧(1%0_2)12和24 h的條件下培養後,應用流式細胞儀檢測CD133錶達暘性細胞的比例,細胞剋隆形成實驗繪製細胞存活麯線以觀察其放射敏感性,採用Western blotting方法測定基因HIF-la及其下遊基因Notch 1蛋白的錶達水平.結果 與常氧培養條件比,SHG44和U251細胞乏氧12和24 h後CD133暘性錶達比例明顯升高;SF_2(2 Gy照射時的存活分數)均升高.在乏氧12和24 h培養時,SHG44細胞株的氧增彊比的值分彆為1.54和1.38.而U251細胞株則分彆為1.44和1.23,提示在乏氧培養時細胞的放射敏感性下降;與常氧培養條件比,乏氧時HIF-la和Notch 1的蛋白錶達水平均明顯升高.結論 微環境乏氧能通過提高腫瘤榦細胞的比例而降低腦膠質瘤細胞的放射敏感性,其可能的作用信號途徑為HIF-la-Notch 1.
목적 탐토미배경핍양시부능통과종류간세포도경인기뇌효질류방사민감성적개변이급가능적상관궤제.방법 선택뇌효질류SHG44화U251세포주분별재상양(20%0_2)、핍양(1%0_2)12화24 h적조건하배양후,응용류식세포의검측CD133표체양성세포적비례,세포극륭형성실험회제세포존활곡선이관찰기방사민감성,채용Western blotting방법측정기인HIF-la급기하유기인Notch 1단백적표체수평.결과 여상양배양조건비,SHG44화U251세포핍양12화24 h후CD133양성표체비례명현승고;SF_2(2 Gy조사시적존활분수)균승고.재핍양12화24 h배양시,SHG44세포주적양증강비적치분별위1.54화1.38.이U251세포주칙분별위1.44화1.23,제시재핍양배양시세포적방사민감성하강;여상양배양조건비,핍양시HIF-la화Notch 1적단백표체수평균명현승고.결론 미배경핍양능통과제고종류간세포적비례이강저뇌효질류세포적방사민감성,기가능적작용신호도경위HIF-la-Notch 1.
Objective To investigate the effect of microenviroment hypoxia on glioma cells radiosensitivity through cancer stem pathway,and to explore the related mechanism.Methods Glioma eell lines SHG44 and U251 were cultured in normoxia (20%0_2) or continuous hypoxia (1%0_2)for 12 and 24 h.The fraction of glioma ceils with positive expression of CD133 was assayed by flow cytometry.The radiosensitivity of glioma cells was determined by clonogenic cell assay.Western blotting was used to investigate the expressions of HIF-la and its downstream gene Notch 1.Resuits The fraction of glioma cells with positive expression of CD133 was higher after hypoxic culture for 12 and 24 h than that of the corresponding cells cultured in normoxia.Compared to the cells cultured in normoxia,SF_2(survival fraction at 2 Gy)were enhanced significantly in SHG44 and U251 cells cultured in hypoxia for 12 and 24 h.The OER (oxygen-enhancement ratio) of SHG44 cells in hypoxia for 12 and 24 h was 1.54 and 1.38,respectively.The OER of U251 cells was 1.44 and 1.23.respectively.The radiosensitivity of these two eell line was decreased in hypoxia.The protein expressions of HIF-la and Notchl genes were elevated more significantly for cells cultured in hypoxia for 12 and 24 h than for those in normoxia.Conclusions Mieroenviroment hypoxia could increase the radioresistance of glioma cells through enrichment of cancer stem cella.and HIF-la-Notchl signal pathway may play an important role in this process.
