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2-甲氧雌二醇对人肺癌细胞的放射增敏作用
引用本文:阎春红,范小航,杨惠玲,陶祥,谢彦,夏云飞,王欣,苏勇,郑芹.2-甲氧雌二醇对人肺癌细胞的放射增敏作用[J].中国病理生理杂志,2010,26(1):137-141.
作者姓名:阎春红  范小航  杨惠玲  陶祥  谢彦  夏云飞  王欣  苏勇  郑芹
作者单位:1中山大学中山医学院病理生理学教研室,广东 广州 510080; 中山大学肿瘤防治中心 2放疗科, 3胸外科, 广东 广州 510060
基金项目:国家自然科学基金资助项目,广东省自然科学基金资助项目,广东省重大科技专项基金资助项目 
摘    要:目的:探讨2-甲氧雌二醇(2-ME)对肺癌细胞A549和GLC-82的放射增敏作用及其对细胞周期的影响,并从分子角度初步探讨2-ME可能的增敏机制。方法:将体外培养的人肺癌细胞A549和GLC-82分为实验组和对照组,其中实验组加入不同浓度的2-ME,对照组不含2-ME。通过MTT法定量检测2-ME对2株细胞增殖的抑制作用,集落形成实验测定2-ME对这2株细胞的放射增敏作用,流式细胞术检测细胞周期分布的变化,通过免疫沉淀法检测细胞周期素依赖性蛋白激酶2(CDK2)活性的改变。结果:分别以2-ME对人肺癌细胞GLC-82和A549的最小有效浓度(0.15625×10-6mol/L和1.25×10-6mol/L)作为放射增敏浓度,均可增加细胞对X线的敏感性,2株细胞存活曲线均见2-ME增敏组比单纯照射组整体下移,D0、Dq值均降低,增敏比:GLC-82细胞为1.98;A549细胞为2.06。细胞周期的检测表明2-ME使细胞周期阻滞于G2/M期,并呈剂量依赖性。2-ME作用后2株细胞CDK2活性均无明显改变。结论:2-ME可通过对细胞周期的调节增加非小细胞肺癌(NSCLC)细胞GLC-82和A549对射线的敏感性。

关 键 词:2-甲氧雌二醇  肺肿瘤  放射敏感性  细胞周期  细胞周期素依赖性蛋白激酶2  
收稿时间:2008-10-17
修稿时间:2009-10-23

Radiosensitizing effect of 2-methoxyestradiol on NSCLC cell lines by blocking cell cycle
YAN Chun-hong,FAN Xiao-hang,YANG Hui-ling,TAO Xiang,XIE Yan,XIA Yun-fei,WANG Xin,SU Yong,ZHENG Qin.Radiosensitizing effect of 2-methoxyestradiol on NSCLC cell lines by blocking cell cycle[J].Chinese Journal of Pathophysiology,2010,26(1):137-141.
Authors:YAN Chun-hong  FAN Xiao-hang  YANG Hui-ling  TAO Xiang  XIE Yan  XIA Yun-fei  WANG Xin  SU Yong  ZHENG Qin
Institution:1Department of Pathophysiology, Zhongshan Medical College of Sun Yat-sen University, Gruangzhou 510080, China; 2Department of Radiotherapy, 3Department of Chest Surgery, Sun Yat-sen University Cancer Center, Guangzhou 510060, China. E-mail: hlyangsums@hotmail.com
Abstract:AIM: To investigate the efficiency of 2-methoxyestradiol (2-ME) as radiosensitizing agent for the treatment of lung cancer cells. METHODS: Cell line A549 and GLC-82 originated from human non-small cell lung cancer were cultured in vitro. Study group (2-ME in different concentrations) and control group without 2-ME were set up. Cell proliferation was measured by MTT assay that lung cancer cells were treated with 2-ME for 24 h, then the cells were exposed from 0 to 8Gy radiation, and the survival fraction was determined by clone forming test. Flow cytometry was used to measure the effects of 2-ME on cell cycle distribution. RESULTS: MTT assay showed minimum effective concentration value was 0.15625×10-6 mol/L in GLC-82 and 1.25×10-6 mol/L in A549 cells. Compared to control group, exposed GLC-82 cells or A549 cells to minimum effective concentration of 2-ME for 24 h before irradiation resulted in an enhancement of radiation. The protection enhancement factor was 1.98 and 2.06 in GLC-82 and A549 cells, respectively. Flow cytometry analysis of cell cycle progression demonstrated G2/M phase arrest in both cells in a dose dependent manner. No obvious change of CDK2 activity in both GLC-82 cells and A549 cells was observed. CONCLUSION: 2-ME enhances radiosensitivity by G2/M phase arrest in the cell cycle.
Keywords:2-methoxyestradiol  Lung neoplasms  Radiosensitivity  Cell cycle  Cyclin-dependent kinase-2
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