中华放射医学与防护杂志

李洁清,宋现让,刘伟,于金明,侯殿俊,马娅,封丽,乔建维.HIF-1α基因沉默对人肺癌放射敏感性及移植瘤生长的影响[J].中华放射医学与防护杂志,2011,31(6):640-643

HIF-1α基因沉默对人肺癌放射敏感性及移植瘤生长的影响

Study on radiosensitivity by targeting HIF-1α in human lung cancer and growth of the transplanted tumors

投稿时间：2011-01-24

DOI：10.3760/cma.j.issn.0254-5098.2011.06.005

英文关键词:Hypoxia HIF-1α Lung cancer Radiosensitivity

基金项目:山东省自然科学基金(ZR2010CM045);山东省医药卫生科技发展计划(2009HZ078)

作者	单位
李洁清	250062 济南,山东省医学科学院放射医学研究所
宋现让	山东省肿瘤医院
刘伟	250062 济南,山东省医学科学院放射医学研究所
于金明	山东省肿瘤医院
侯殿俊	250062 济南,山东省医学科学院放射医学研究所
马娅	250062 济南,山东省医学科学院放射医学研究所
封丽	250062 济南,山东省医学科学院放射医学研究所
乔建维	250062 济南,山东省医学科学院放射医学研究所

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中文摘要:

目的探讨HIF-1α基因沉默对A549肺癌细胞放射敏感性及裸鼠移植瘤生长的影响。方法采用克隆形成实验,评价A549/HIF-1α(-)细胞及A549细胞对X射线的敏感性。将A549/HIF-1α(-)细胞及A549细胞接种于BALB/C雄性裸小鼠,观察肿瘤生长情况。免疫组织化学法检测肿瘤内HIF-1α蛋白的表达及瘤内微血管密度。结果 HIF-1α基因沉默在常氧条件下放射增敏比 (SER) 为1.06,乏氧条件下为1.65。A549/HIF-1α(-)组移植瘤体积明显小于A549组,A549/HIF-1α(-)组肿瘤细胞HIF-1α蛋白表达显著下降, A549组肿瘤微血管密度为19.83±4.09,而A549/HIF-1α(-)组为11.61±3.04(F=15.57,P<0.05)。结论 HIF-1α基因沉默可以逆转乏氧诱导的A549肺癌细胞对X射线敏感性的降低,并延缓裸鼠移植瘤的生长,使HIF-1α蛋白表达下降和血管生成减少。

英文摘要:

Objective To observe the radiosensitivity by targeting HIF-1α in human lung cancer and the effects on tumor growth in nude mice. Methods Radiosensitivity of A549 and A549/HIF-1α(-) cells were tested by clonogenic forming assay. A549/HIF-1α(-) cells and A549 cells were injected into the male BALB/C nude mice. Tumor growth was observed. The expression of HIF-1α and microvessel density were detected by immunohistochemistry method. Results SERs of HIF-1α gene silencing were 1.03 in normoxia and 1.65 in hypoxia. The sizes of tumor xenografts derived from A549/HIF-1α(-) cells were significantly reduced compared to those of the xenografts derived from A549 cells. HIF-1α protein staining result showed a dramatic decrease in tumors from A549/HIF-1α(-) mice. The microvessel densities (MVD) were 19.83 ± 4.09 in A549 group and 11.61±3.04 in A549/HIF-1α (-)group(F=15.57,P<0.05). Conclusions Hypoxia-induced radio-resistance in lung cancer A549 cells could be reversed by silencing the HIF-1α. It also retards the growth of tumor xenografts, decreases HIF-1α expression and reduces the vascularity.

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