氟达拉滨联合不同电离辐射对肾癌细胞系786-O杀伤效果观察  

Cellular response to fludarabine treatment in combination with different ionizing radiation in renal carcinoma 786-O cells

作　　者：宋雷[1] 刘勇[2] 马伟林[3] 陈林林[4] 郭忠[1] 

机构地区：[1]西北民族大学医学院机能学教研室,兰州730030 [2]西北民族大学医学院生化教研室,兰州730030 [3]西北民族大学医学院临床医学系,兰州730030 [4]西北民族大学医学院护理学系,兰州730030

出　　处：《中华放射肿瘤学杂志》2016年第6期646-651,共6页Chinese Journal of Radiation Oncology

基　　金：基金项目：国家自然科学基金项目（81560508）;中央高校基本科研业务费专项资金（31920160009）;国家级大学生创新创业训练项目（201410742058）

摘　　要：目的 比较氟达拉滨（FA）联用不同电离辐射对肾癌细胞系786-O的DNA双链损伤作用异同和药物放射增敏效应。方法 FA联用X射线、重离子处理786-O细胞,流式细胞术检测γH2AX细胞分数和周期分布,中性彗星电泳法检测细胞DNA双链损伤程度,克隆形成法比较不同处理对细胞存活影响。单因素方差分析或Dunnet’s t检验比较组间差异。结果 与单纯给药和单纯照射相比,FA联合不同电离辐射可增强细胞DNA双链损伤程度,表现为γH2AX水平均显著提高（P=0.007、0.001）;重离子联用则可将细胞周期阻滞在放射敏感时相G2＋M期（P=0.020、0.060）,并显著增加G2＋M期γH2AX表达量（P=0.000、0.000）;彗星电泳表明DNA亚致死性损伤随着药物与射线的联合应用而显著增加（P=0.030、0.020;0.020、0.030）;FA可降低放射后细胞克隆形成率（P=0.000、0.030;0.001、0.040）。结论 FA增强X射线和重离子束的放射效应具有不同特点,其增强重离子束的放射杀伤作用尤为明显。Objective To investigate DNA double-strand breaks and radiosensitization in renalcarcinoma 786-O cells induced by fludarabine （FA） combined with different ionizing radiations. Methods The 786-O cells were exposed to FA combined with X-ray or heavy ion beam irradiation. Flow cytometry was used to evaluate the percentage of γH2AX-positive cells and cell cycle. The neutral comet assay was used to detect DNA double-strand breaks. The colony-forming assay was used to evaluate the effects of different treatments on cell survival. Comparison between groups was made by one-way analysis of variance or Dunnet’s t test. Results Compared with FA alone or irradiation alone, FA combined with different ionizing radiations increased DNA double-strand breaks as shown by significantly increased levels of γH2AX （P=0.007,0.001）;FA combined with heavy ion beam irradiation lead to a cell cycle block at the radiosensitive G2/M phase and significantly increased the expression of γH2AX in the G2/M phase （P=0.000,0.000）;the neutral comet assay revealed that FA combined with irradiation significantly increased DNA sublethal damage （P=0.020,0.060）;FA significantly reduced the colony-forming rate after irradiation （P=0.000,0.030;0.001,0.040）. Conclusions FA enhances the effects induced by X-ray and heavy ion beam irradiation with different properties. Particularly, FA substantially enhances the cell death induced by heavy ion beam irradiation.

关 键 词：脱氧核糖核酸损伤 氟达拉滨 重离子束 X射线 786-O细胞系 

分 类 号：R737.11[医药卫生—肿瘤]