孙新臣,王俊杰,甄永苏,邵荣光.粉防己碱增加人乳腺癌细胞对X射线敏感性及其机理研究[J].中华放射医学与防护杂志,2003,23(3):160-162
粉防己碱增加人乳腺癌细胞对X射线敏感性及其机理研究
Potentiation of radiosensitivity by tetrandrine in human breast cancer cells and its mechanism
投稿时间:2002-04-12  
DOI:
中文关键词:  粉防己碱  增敏作用  X射线  p53
英文关键词:Tetrandrine  Sensitivity  X-ray  p53
基金项目:国家杰出青年基金资助项目(30025043);国家自然科学基金资助项目(3947001);美国肿瘤基金会(NFCR)基金资助项目
作者单位E-mail
孙新臣 100050 北京, 中国医学科学院中国协和医科大学医药生物技术研究所 shaor@public3.bta.net.cn 
王俊杰 北京大学第三医院肿瘤治疗中心  
甄永苏 100050 北京, 中国医学科学院中国协和医科大学医药生物技术研究所  
邵荣光 100050 北京, 中国医学科学院中国协和医科大学医药生物技术研究所  
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中文摘要:
      目的 研究粉防己碱(Tet)与X射线对人乳腺癌细胞的作用和机理。方法 采用克隆形成分析法,流式细胞术,Western Blotting以及分裂指数法进行实验。结果 在p53突变型MCF-7/ADR细胞中,Tet显著增加X射线的杀伤作用,其增敏比为1.51;在X射线照射后,细胞明显阻滞于G2期,Tet可以降低这种阻滞。而在p53野生型MCF-7细胞中,Tet增加X射线的杀伤作用不明显,增敏比为1.10;在X射线照射后,细胞阻滞于G1期,部分阻滞于G2期,加入Tet,对于这种阻滞作用降低也不明显。进一步研究显示,MCF-7/ADR细胞在受到X射线照射后,其CyclinB1与Cdc2蛋白表达水平明显降低;Tet可以逆转X射线对Cyclin B1与Cdc2蛋白的表达的抑制作用。分裂指数结果显示Tet可以促使阻滞于G2期的MCF-7/ADR细胞进入M期。结论 Tet是一种G2期阻滞清除剂,能显著增加X射线对人乳腺癌细胞的杀伤作用,这种作用在p53突变型细胞中更明显。
英文摘要:
      Objective To investigate the potentiation of radiosensitivity and mechanism by tetrandrine (Tet) in human breast cancer p53-mutant MCF-7/ADR and p53-wt MCF-7 cells. Methods Clonogenic assay, flow cytometry, Western blotting were preformed in this experiment. Results The data of clonogenic assay showed that Tet markedly sensitized MCF-7/ADR cell to X-rays, and the sensitization enhancement ratio (SER) of Tet was 1 51.Flow cytometry assay showed that exposure of MCF-7/ADR cells to X-rays caused cells to arrest in G2 phase, whereas Tet was able to lower the number of cells arrested in G2 phase.However, in MCF-7 cells, the potentiation effect of Tet was lower, and its SER was 1 10.MCF-7 cells were induced to arrest in G1 and G2 phases by X-rays, and the number of cells arrested in G2 phase abrogated by Tet was less than that in MCF-7/ADR cells.Furthermore, the results showed that the levels of Cyclin B1 and Cdc2 expression decreased after X-irradiation, and the mitotic index was lower too.Tet could reverse this decrease and induce X-ray-irradiated cells to enter mitosis. Conclusion Tet is a potent G2 checkpoint abrogator and markedly enhances the cytotoxicity of X irradiation in the p53-mutant cancer cells.
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