盐霉素对鼻咽癌CNE-2细胞放射敏感性的影响

目的:体外实验研究盐霉素对鼻咽癌CNE-2细胞放射敏感性的影响。方法:通过CCK-8法检测盐霉素作用后鼻咽癌CNE-2细胞的增殖情况。利用克隆集落形成实验观察鼻咽癌细胞成活情况，单击多靶模型拟合剂量存活曲线，计算放射增敏指数（SER）；Chou-Talalay数学模型绘制联合指数（CI）曲线，判断盐霉素和放射的作用关系。利用γ-H2AX焦点形成检测DNA分子损伤情况。结果:盐霉素能够抑制鼻咽癌细胞的增殖，并且具有明显的时间和剂量依赖性；盐霉素作用鼻咽癌细胞的IC50值在24 h时为17.81 μmol/L，48 h时为3.98 μmol/L。根据单击多靶模型拟合细胞的存活曲线，可知在鼻咽癌细胞CNE-2中盐霉素浓度为0.1 μmol/L和0.5 μmol/L时SER分别为1.19和1.21，均大于1.0，表明盐霉素对鼻咽癌细胞具有明显的放射增敏作用。制作联合指数（CI）曲线，可知在盐霉素浓度为0.1 μmol/L时，放射剂量为2 Gy时，CI值≈1，盐霉素和放射对CNE-2的作用接近相加作用，放射剂量为4、6、8 Gy时，CI值均＜1，二者为协同作用；在盐霉素浓度为0.5 μmol/L时，放射剂量为2、4、6、8 Gy时，CI值均＜1，二者均为协同作用。相对于照射组，盐霉素+照射组能增加DNA损伤数目。结论:盐霉素能提高鼻咽癌细胞的放射敏感性，为一种潜在的放射增敏药物。

Salinomycin enhances the radioresponse in human nasopharyngeal carcinoma cell lines CNE-2

Objective:To evaluate whether salinomycin can change the sensitivity of nasopharyngeal carcinoma cell line CNE-2 to radiotherapy.Methods:The proliferation of CNE-2 cells treated with salinomycin was detected by CCK-8.The cell survival curves were determined by cloning assay and cell clone technique for evaluating the cell lethal effects through multitarget one-lit model.The combination index (CI) curve was drawn by Chou-Talalay method to judge the interaction between salinomycin and radiation.DNA damage was detected by γ-H2AX foci counting.Results:The salinomycin inhibited the growth of CNE-2 in time- and dose-dependent manner.At 24 h,the IC50 of salinomycin on CNE-2 cells was 17.81 μmol/L.At 48 h,the IC50 of salinomycinon on CNE-2 cell lines was 3.98 μmol/L.The sensitizing enhancement ratio (SER) was 1.19 for CNE-2 cells which were treated by salinomycin of 0.1 μmol/L.After treatment with salinomycin with 0.5 μmol/L,SER was 1.21.Both were greater than 1.0,it indicated that salinomycin had obvious radiosensitization effect on nasopharyngeal carcinoma cells.The CI values of salinomycin (0.1 μmol/L) was ≈1 when combined with radiation (2 Gy),indicated an additivity effect,while the CI values of salinomycin (0.1 μmol/L) were both < 1 when combined with radiation (4,6,8 Gy) indicated a synergy effect.The CI values of salinomycin (0.5 μmol/L) were both < 1 when combined with radiation (2,4,6,8 Gy),indicated a synergy effect.Compared with the radiation alone group,salinomycin (0.5 μmol/L) combined with radiation (4 Gy) induced more DNA double chain breaks.Conclusion:We provided evidence in vitro that salinomycin enhances radiosensitivity of CNE-2 cells.Salinomycin appears to be a potential radiotherapy sensitization agent for nasopharyngeal carcinoma treatment.