李洁清,宋现让,于金明,等.HIF-1α基因沉默对A549肺癌细胞放射敏感性的影响[J].中华放射医学与防护杂志,2008,28(2):120-123.LI Jie-qing,SONG Xian-rang,YU Jin-ming,et al.Analysis of radiosensitivity of A549 lung cancer cells with HIF-1α silencing by RNAi[J].Chin J Radiol Med Prot,2008,28(2):120-123
HIF-1α基因沉默对A549肺癌细胞放射敏感性的影响
Analysis of radiosensitivity of A549 lung cancer cells with HIF-1α silencing by RNAi
投稿时间:2007-08-13  
DOI:
中文关键词:  乏氧  HIF-1α  RNA干扰  放射敏感性
英文关键词:Hypoxia  HIF-1α  RNAi  Radiosensitivity
基金项目:国家自然科学基金资助项目(30570547)
作者单位E-mail
李洁清 300070 天津医科大学肿瘤医院  
宋现让 基础研究中心  
于金明 山东省肿瘤医院放疗 jn7984729@public.jn.sd.cn 
魏玲 基础研究中心  
王兴武 基础研究中心  
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中文摘要:
      目的 探讨RNA干扰技术致HIF-1α基因沉默对裸鼠肺癌种植瘤放射敏感性的影响。方法 采用以慢病毒为载体的RNA干扰技术获得HIF-1α基因沉默的A549肺癌细胞株,用Western blot方法检测HIF-1α蛋白的表达。将A549/HIF-1α(-)细胞及A549细胞接种于4~6周BALB/C雄性裸小鼠,观察肿瘤生长情况。肿瘤体积达200~350 mm3时分别给予局部单次5、10、15和20 Gy X射线照射,观察对照组和照射组肿瘤体积和肿瘤生长延缓时间。结果 在常氧和乏氧状态下,A549/HIF-1α(-)细胞HIF-1α蛋白表达水平均显著下降,A549/HIF-1α(-)组裸鼠成瘤潜伏期较长,肿瘤生长慢于A549组(P<0.05),X射线照射对两种裸鼠种植瘤的生长均有抑制作用,但A549/HIF-1α(-)组肿瘤生长延缓显著。结论 RNA干扰技术能稳定阻断人肺腺癌A549细胞HIF-1α表达,HIF-1α基因沉默的肿瘤细胞对X射线照射更敏感。
英文摘要:
      Objective To observe the effect of HIF-1α silencing on human lung cancer cells radiosensitivity in nude mice.Methods A549/HIF-1α(-) cell line was established by RNAi with lentivirus as vector. The expression of HIF-1α protein was analyzed by Western Blot. A549/HIF-1α(-) cells and A549 cells were injected into the male BALB/C nude mice aged 4_6 weeks.The tumors were locally irradiated with single doses (5,10,15 and 20 Gy) of X-ray irradiation when tumor sizes reached 200_350 mm3. The volumes of tumor were measured every 3 days.Time of the tumor growth delay was caculated.Results The expression of HIF-1α protein of A549/HIF-1α(-) cells was inhibited significantly under both normoxia and hypoxia condition.A549/HIF-1α(-) tumors reproduced more slowly than A549 tumors(P<0.05). X-ray radiation could inhibit tumor growth of all groups. The growth delay of A549/HIF-1α(-) tumors was more significant than of A549 tumors(P<0.05).Conclusions The expression of HIF-1α can be stably blocked by RNAi. A549/HIF-1α(-) tumors appear to be more radiosensitive than A549 tumors.
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