β-榄香烯对胃癌MKN28细胞株放射增敏作用的研究  

Enhancement of gastric cancer MKN28 cell line radiosensitivity induced by β-elemene

作　　者：贺仕才[1] 刘俊松[1] 张正良[1] 车向明[1] 樊林[1] 常帅[1] 仇广林[1] 赵伟[1] 

机构地区：[1]西安交通大学医学院第一附属医院普通外科,710061

出　　处：《中华外科杂志》2014年第6期442-445,共4页Chinese Journal of Surgery

基　　金：国家自然科学基金资助项目（81172357）

摘　　要：目的 研究β-榄香烯对胃癌MKN28细胞的放射增敏作用及其作用机制.方法 选用对数生长期的人胃癌细胞株MKN28,MTT法检测细胞增殖抑制率,计算IC50以筛选实验药物浓度.通过平板克隆形成实验计算细胞存活分数,根据多靶单击模型绘制放射生存曲线,计算各放射生物学参数平均致死剂量（D0）、准域剂量（Dq）、外推数（N）、照射2Gy时细胞存活率（SF2）和放射增敏比（SER）.用流式细胞仪检测细胞周期变化和凋亡率.结果 β-榄香烯对MKN28胃癌细胞株增殖抑制作用呈浓度依赖性,24 h IC50为45.6 mg/L,采用接近20％ IC50浓度8 mg/L作为实验浓度.克隆形成实验发现,联合组放射生存曲线左移,直线部分斜率增大,肩区明显缩小,D0值、Dq值较单纯放射组均明显下降（SER=1.3）.流式细胞仪检测发现,β-榄香烯可以阻滞MKN28胃癌细胞于放射相对敏感的G2/M期.用Annexin-V/PI法检测细胞凋亡发现,β-榄香烯和放射联合作用明显提高细胞凋亡率,与放射组和对照组差异均有统计学意义（P＜0.05）.结论 β-榄香烯对胃癌MKN28细胞具有放射增敏作用,其机制可能是通过β-榄香烯引起G2/M期阻滞,抑制亚致死性损伤的修复和诱导凋亡实现的.Objective To study radiation-enhancing effects on human gastric cancer MKN28 cell line and underlying mechanisms of β-elemene.Methods Inhibition of MKN28 cell proliferation at different concentrations of β-elemene was assessed using the methyl thiazolyl blue colorimetric method （MTT method）,with calculation of IC50 value and choice of 20％ of the IC50 as the experimental drug concentration.Irradiation group and β-elemene ＋ irradiation group were established,and the cell survival fraction （SF） was calculated from flat panel colony forming analysis,and fitted by the ‘ multitarget click mathematical model＇.Draw the survival curve and get the radiobiological parameters D0,Dq,SF2,N and SER.Flow cytometry （FCM） was used to detect changes in the cell cycle and cell apoptosis rates was detected by Annexin-V/PI assay.Results β-elemene exerted inhibitory effects on proliferation of gastric cancer MKN28 cells,with an IC50 of 45.6 mg/L and we chose 8 mg/L as the experimental concentration.The cell survival fraction of MKN28 cells with irradiation decreased significantly after treated with β-elemene; D0,Dq decreased,SER =1.3.After combined treatment of β-elemene ＋ irradiation,the results of FCM showed that cells could be arrested in the G2/M phase and the cell apoptosis increased significantly.Conclusions β-elemene can enhance the radiosensitivity of gastric cancer MKN28 cell line.Mechanistically,β-elemene mainly influences the cell cycle distribution of MKN28 cells by inducing G2/M phase arrest,inhibits the repair of sublethal damage and induces cell apoptosis to enhance the killing effects of radioactive rays.

关 键 词：胃肿瘤 细胞系 肿瘤 莪术烯酮 辐射增敏药 

分 类 号：R735.2[医药卫生—肿瘤]