UCN-01增加鼻咽癌细胞放射敏感性的相关机制  

Mechanism of radiosensitization of UCN-01 in nasopharyngeal cancer cells

作　　者：惠周光[1] 李晔雄[1] 杨伟志[1] 高远红[1] 余子豪[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院放疗科,北京100021

出　　处：《中华放射肿瘤学杂志》2006年第1期46-49,共4页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金委重点项目资助项目(10335050)

摘　　要：目的在前期研究基础上,进一步探讨UCN-01增加鼻咽癌细胞放射敏感性的相关机制。方法应用流式细胞仪和凋亡试剂盒测定不同条件下CNE-1细胞的凋亡比例。应用彗星分析法测定不同实验组肿瘤细胞在照射后不同时间的DNA损伤程度,用以观察UCN-01对CNE-1细胞修复DNA损伤能力的影响。结果照射+UCN-01组与单纯照射组相比,细胞总凋亡比例仅有轻微增加(14.9%∶13.6%),其中主要表现为早期凋亡比例轻度增加(5.0%∶3.9%),两组细胞晚期凋亡比例相仿(9.9%∶9.7%),细胞凋亡不是UCN-01对CNE-1细胞放射增敏的主要机制。照射后加入UCN-01组细胞的尾力矩下降速度较单纯照射组明显降低,即DNA的修复速度降低,两组的半修复时间分别为3.1、0.4 h,说明UCN-01使CNE-1细胞修复放射性DNA损伤的能力下降。结论UCN-01未明显增加放射后CNE-1细胞的凋亡比例;UCN-01使细胞修复放射性DNA损伤的能力降低可能是该药放射增敏的重要机制之一。Objective Based on the former study, radiosensitization mechanism of 7-Hythroxystaurosporine （UCN-01） in nasopharyngeal cancer cell is further investigated. Methods Human nasopharyngeal carcinoma ceil line CNE-1 with p53 mutation, was used in this study. The effect of UCN-01 on apoptosis in irradiated CNE- 1 cells was determined by flow cytometry after the ceils had been dyed by annexin V and propidium iodide （PI）. The effect of UCN-01 on DNA damage repair ability of CNE-1 ceil was measured by Comet assay. Results In CNE-1 ceil, the total percentage of apoptotic ceils was only slightly increased in irradiation plus UCN-01 group when compared with irradiation alone group （14.9%：13.6%）, and most of which was due to the slight increase in early apoptosis （5.0%：3.9% ）. The percentage of later apoptotic cells was comparable between the two groups （9.9% ：9.7% ）. The decrease of tail moment, which shows the DNA damage repair ability, was obviously slower in radiation plus UCN-01 group than the radiation alone group. UCN-01 did abate the ceil ability of DNA damage repair with a half repair time of 0.4h and 3.1h in the two groups. Conclusions UCN-01 is not able to increase the radiation-induced CNE-1 cell apoptosis. Repair inhibition of radiation-induced DNA damage should be an important radiosensitization mechanism of UCN-01.

关 键 词：放射增敏药 细胞凋亡 彗星分析法 细胞系 肿瘤 

分 类 号：R739.63[医药卫生—肿瘤]