2-甲氧雌二醇对人肺癌细胞的放射增敏作用  

Radiosensitizing effect of 2-methoxyestradiol on NSCLC cell lines by blocking cell cycle

作　　者：阎春红[1] 范小航[1] 杨惠玲[1] 陶祥[1] 谢彦[1] 夏云飞[2] 王欣[3] 苏勇[2] 郑芹[1] 

机构地区：[1]中山大学中山医学院病理生理学教研室,广东广州510080 [2]中山大学肿瘤防治中心放疗科,广东广州510060 [3]中山大学肿瘤防治中心胸外科,广东广州510060

出　　处：《中国病理生理杂志》2010年第1期137-141,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30670627);广东省自然科学基金资助项目(No.06021210);广东省重大科技专项基金资助项目(No.2004A30801006)

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。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 ： MTr 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.

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 

分 类 号：R739.6[医药卫生—肿瘤]