游震宇,赵勇,江萍,等.血管内皮抑素联合照射对肺癌H-520细胞周期及信号传导通路的影响[J].中华放射医学与防护杂志,2010,30(3):287-290.YOU Zhen-yu,ZHAO Yong,JIANG Ping,et al.Mechanism of radiosensitizing effects of endostatin on H-520 human lung squamous cancer cells[J].Chin J Radiol Med Prot,2010,30(3):287-290
血管内皮抑素联合照射对肺癌H-520细胞周期及信号传导通路的影响
Mechanism of radiosensitizing effects of endostatin on H-520 human lung squamous cancer cells
投稿时间:2009-07-13  
DOI:10.3760/cma.j.issn.0254-5098.2010.03.015
中文关键词:  血管内皮抑素  肺鳞癌  放射增敏  p38-MAPK  Akt
英文关键词:Endostatin  Lung squamous cancer  Radiosensitization  p38-MAPK  Akt
基金项目:
作者单位E-mail
游震宇 100191, 北京大学第三医院肿瘤治疗中心放疗科  
赵勇 中国科学院动物研究所生物膜与膜生物工程国家重点实验室  
江萍 100191, 北京大学第三医院肿瘤治疗中心放疗科  
孟娜 100191, 北京大学第三医院肿瘤治疗中心放疗科  
王俊杰 100191, 北京大学第三医院肿瘤治疗中心放疗科 doctorjunjiewang@yahoo.com.cn 
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中文摘要:
      目的 探讨血管内皮抑素对肺鳞癌细胞系H-520细胞放射增敏作用的机制。 方法 重组人血管内皮抑素联合60Co γ线作用于H-520细胞后,集落形成实验检测重组人血管内皮抑素对H-520细胞的放射增敏作用;流式细胞术检测细胞周期变化及磷酸化p38-MAPK蛋白的表达水平;RT-PCR检测周期相关基因cyclin D1、cdk2、cdk4及凋亡相关基因survivin的表达情况;Western-blotting检测磷酸化Akt蛋白表达情况。结果 血管内皮抑素可以增加细胞对60Co γ射线的放射敏感性,联合组D0DqND10SF2较照射组低,放射增敏比为1.45;200 μg/ml血管内皮抑素处理后H-520细胞发生G0/G1期阻滞,周期相关基因cyclin D1、cdk2、cdk4及凋亡相关基因survivin表达下降;血管内皮抑素联合照射后磷酸化p38-MAPK蛋白及磷酸化Akt蛋白表达下降。结论 血管内皮抑素可能通过抑制H-520细胞增殖,诱导细胞发生G0/G1期阻滞,促进细胞凋亡及阻断p38-MAPK和PI3K/Akt信号通路传导,发挥放射增敏作用。
英文摘要:
      Objective To investigate the mechanism of radiosensitizing effects of endostatin on H-520 human lung squamous cancer cells.Methods H-520 cells was treated with endostatin and/or radiation.Colony-forming assays were used to indicate the radiosensitising effects. Cell cycle distribution and expression of phosphor-p38-MAPK were assayed by FCM, and cyclin D1, cdk2, cdk4 and survivin mRNA levels were assayed by RT-PCR. Phosphor-Akt was evaluated by Western-blotting.Results Combination of endostatin and irradiation inhibited the proliferation of H-520 cells. According to the colony-forming assays, the D0, Dq, D10 and SF2 values of the combination groups were much lower than those of irradiation groups. The sensitization enhancement ratio (SER) was 1.51. G2/M arrest occurred after 4 Gy irradiation. The gene expression of cyclin D1, cdk2, ckd4 and survivin and phosphor-Akt protein were down-regulated after treatment. The expression of phosphor-p38-MAPK protein was also down-regulated after treatment with 200 μg/ml endostar.Conclusions Endostatin inhibits the growth of H-520 cells and radiosensitizes the cells by induction of G0/G1arrest, cell apoptosis and down-regulation of gene expression of cyclin D1, cdk2, cdk4 and reduces the phosphorylation of Akt and p38-MAPK.
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