庞得全,王佩国,王平,张维铭.外源性野生型p53基因对不同p53功能状态的人肺腺癌细胞株的放射增敏作用[J].中华放射医学与防护杂志,2008,28(1):38-41
外源性野生型p53基因对不同p53功能状态的人肺腺癌细胞株的放射增敏作用
Enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell with different p53 status
投稿时间:2007-04-24  
DOI:
中文关键词:  肺腺癌  腺病毒载体  p53  放射增敏
英文关键词:Lung adenocarcinoma  Adenovirus vector  p53  Radiosensitivity
基金项目:
作者单位E-mail
庞得全 300070 天津医科大学附属肿瘤医院、天津市肿瘤防治重点实验室  
王佩国 300070 天津医科大学附属肿瘤医院、天津市肿瘤防治重点实验室 wangpeiguo@yahoo.com.cn 
王平 300070 天津医科大学附属肿瘤医院、天津市肿瘤防治重点实验室  
张维铭 天津医科大学实验中心  
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中文摘要:
      目的 观察外源性野生型p53基因(wtp53)对人肺腺癌细胞株的放射增敏作用,比较不同p53基因状态对照射的影响。 方法 免疫组织化学法、聚合酶链反应-单链构象多态性分析(PCR-SSCP法)筛选p53基因状态不同的两种人肺腺癌细胞系A549及GLC-82,用腺病毒介导wtp53 (Ad-p53)转染后分别给予0、2和4 Gy照射,测定集落形成率,流式细胞仪检测细胞周期分布和凋亡。结果 A549细胞的p53基因正常,而GLC-82细胞的p53基因第7外显子突变,转染后wtp53在两种细胞内均成功表达。Ad-p53对A549及GLC-82细胞抑制率分别为55%和88%,对GLC-82抑制作用较强(P<0.01)。转染Ad-p53后照射,两种细胞集落形成率较对照组明显下降(P<0.001)。流式细胞仪分析Ad-p53使G1期细胞比例增加和凋亡指数增高,Ad-p53+照射组最为明显(P<0.001)。结论 Ad-wtp53可以抑制人肺腺癌细胞株的生长,增加其放射敏感性,其放射增敏作用并不依赖于细胞内源性p53基因的状态。
英文摘要:
      Objective To investigate the enhancement of radiosensitivity of recombinant Ad-p53 gene on human lung adenocarcinoma cell lines( A549 and GLC-82) with different p53 status in vitro. Methods Two human lung adenocarcinoma cell lines of A549 and GLC-82 were examined on their difference in p53 status with immunohistochemistry stain and PCR-SSCP technique. Expand Ad-wtp53 was transfected into tumor cells. Clonogenic assays were performed to evaluate the inhibition effect on cell growth and the degree of sensitization to irradiation. Apoptosis and cell cycle changes were determined using the flow cytometry assay. Results The A549 cell line presented positive P53 expression while GLC-82 negative. GLC-82 bore mutant p53 on the exon 7. The wtp53 gene could be efficiently expressed in the two cell lines and greatly inhibit the cell growth. Its efficiency didn't depend on the intrinsic p53 genetic status. After irradiation, its function of inducing G1 arrest and apoptosis on GLC-82 cell line was much stronger than the A549 cell line. In both the A549 and GLC-82 cell lines, the combination of Ad-p53 plus radiation resulted in more apoptosis than the others. There was no significant difference between two groups.Conclusions Ad-p53 can depress the tumor growth and enhance the radiosensitivity of human lung adenocarcinoma cells. And this effect is independent of endogenous p53 status.
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