Doranidazole对乏氧胰腺癌细胞放射增敏研究  

Doranidazole in the radiosensitization of hypoxic pancreatic cancer cells

作　　者：张利[1] 李树连 纪军[1] 

机构地区：[1]大连大学附属中心医院中心实验室,116033 [2]辽宁省抚顺市清原县人民医院,113300

出　　处：《中华放射肿瘤学杂志》2004年第4期319-323,共5页Chinese Journal of Radiation Oncology

摘　　要：目的　研究新一代硝基咪唑衍生物 Doranidazole在低氧环境下对胰腺癌细胞的放射增敏效果。方法　在低氧和加Doranidazole环境下对人胰腺癌细胞系施行单次大剂量γ线照射 ,通过微孔板荧光酶标仪检测细胞死亡率来研究放射增敏作用。细胞死亡的增敏效果从时间相关性及形态学方面进行评价。Doranidazole在低氧环境下的选择性增敏效果利用流式细胞技术进行验证。结果　在7种胰腺癌细胞系中 ,5种细胞实行 30Gy大剂量照射 5d后的细胞死亡率在低氧环境下因Doranidazole的添加而显著增高 ;而常规环境下却无明显的增敏作用。同时提示Doranidazole在低氧环境下的选择性增敏作用有时间相关性。Objective To investigate the effects of a new radiosensitizer, nitroimidazole-derivative--Doranidazole on pancreatic cancer cells under hypoxic condition. Methods The human pancreatic cancer cell lines were exposed in vitro to a single fraction of high doseγ-ray radiation either with doranidazole or under hypoxic condition. The percentage of dead cells was analyzed with a multiwell plated reader and the fluorescence intensities of propidium iodide before and after a digitonin tratment were measured. The sensitizing effect of doranidazole on cell killing by high-dose irradiation was evaluated by time-course, dose-dependency, and microscopic observations. The selective radiosensitive effect of doranidazole on hypoxic cells was evaluated by flow cytometry. Results Of seven pancreatic cancer cell lines, the mortalities of 5 cell lines were significantly increased in presence of doranidazole under hypoxic condition 5 days after 30 ?Gy irradiation, but not under aerobic condition. Meanwhile, the radiosensitizing effect of Doranidazole on pancreatic cancer cells was demonstrated as time- and dose-dependent manner. Conclusion Doranidazole can enhance the radiosensitivity on pancreatic cancer cells under hypoxic condition with high-dose irradiation.

关 键 词：Doranidazole 乏氧胰腺癌细胞 放射增敏 辐射增敏药 细胞死亡 

分 类 号：R735.9[医药卫生—肿瘤]