盐酸小檗碱对乏氧食管癌细胞的放射增敏作用  

Radiosensitivity of berberine on hypoxia esophageal cancer cells

作　　者：杨百霞[1] 杨曦[1] 朱琪伟[1] 吴志军[1] 翟小刚[1] 夏小春[1] 蔡晶[1] 

机构地区：[1]南通市肿瘤医院,226361

出　　处：《中华放射医学与防护杂志》2013年第5期484-488,共5页Chinese Journal of Radiological Medicine and Protection

摘　　要：目的研究盐酸小檗碱对乏氧食管癌细胞的放射增敏作用。方法通过MTT法检测盐酸小檗碱对食管癌ECA-109细胞生长的抑制；克隆集落形成实验观察盐酸小檗碱的放射增敏作用；通过免疫荧光实验观察HIF．1的表达情况；流式细胞仪检测细胞的凋亡情况；Westernblot检测细胞内HIF-1表达；1-H2AX焦点形成检测DNA分子损伤情况。结果盐酸小檗碱抑制食管癌ECA-109细胞的生长，并且有明显的时间和剂量依赖性；通过单击多靶模型拟合曲线，可见低浓度盐酸小檗碱预处理24h，相比于照射组，可以增加乏氧ECA-109细胞的辐射敏感性（t=3．69，P〈0．05），辐射增敏指数为1．42；与照射组相比，盐酸小檗碱＋照射组中的细胞凋亡率明显增加（t=4．74，P〈0．05）；盐酸小檗碱作用于乏氧食管癌细胞，可以使乏氧相关蛋白HIF-1的表达降低，并且呈现明显的量效关系；相对于照射组，盐酸小檗碱＋照射组能够增加DNA双链断裂数目（DSB）。结论盐酸小檗碱能够提高食管癌细胞的放射敏感性，与其增加食管癌细胞的凋亡率和降低乏氧食管癌ECA-109细胞内HIF-1的表达有关。Objective To explore the radiosensitivity of berberine on esophageal cancer cells under hypoxia condition. Methods MTT assay and clonogenic survival assay were used to evaluate the effect of berberine on proliferation inhibition and radiosensitivity of esophageal cancer cells, respectively. Immunofluorescence was employed to examine the expression of HIF-1. The change of cell cycle distribution and cell apoptosis was assayed by flow cytometry. The expression of HIF-1 was measured by Western blot. DNA damage was detected by T-H2AX Foci counting. Results With a clear dose and time effect, berberine inhibited cell proliferation and enhanced cell radiosensitivity （ t = 3.69, P 〈 0. 05 ） with a sensitizing enhancement ratio （SER） of 1.42. Berberine caused a dose-dependent decrease in HIF-! protein expression and also significantly increased the cell apoptosis in ECA-109 population （t = 4.74 ,P 〈 0. 05）. Compared with the radiation alone group, berberine enhanced X-ray induced DNA double chain breaks （DSB）. Conclusions Berberine can increase the radiosensitivity of esophageal cell line ECA-109, which may be associated with decrease of HIF-1 expression and induction of apoptosis in ECA-109 ceils.

关 键 词：盐酸小檗碱 食管癌 乏氧 HIF-1 放射敏感性 

分 类 号：R735.1[医药卫生—肿瘤]