依西美坦联合同期或序贯放射对MCF-7细胞放射敏感性的影响

背景与目的：放疗和内分泌治疗是乳腺癌术后辅助治疗的重要组成部分，但关于二者相互作用的研究较少。辅助放疗和内分泌治疗的最佳时序至今尚无定论，而两者的时序安排对临床却非常重要。本研究通过探讨依西美坦同期或序贯放射对人乳腺癌MCF-7细胞株放射敏感性的影响及其可能的机制，为临床制定最佳的治疗模式提供理论依据。方法：将人乳腺癌MCF-7细胞株分成单纯放射组、放射前加依西美坦组和放射后加依西美坦组，采用克隆形成试验法检测各组的放射敏感性，用MTT法检测各组的细胞增殖率，用DAPI染色法检测各组的细胞凋亡率，用蛋白[质]印迹法(Western blot)检测各组Bcl-2和Bax蛋白的表达情况。结果：放射前加依西美坦组和放射后加依西美坦组的放射增敏比(sensitive enhancement ratio，SER)分别为1.51和1.37；与单纯放射组相比，依西美坦联合放射组肿瘤细胞抑制率和细胞凋亡率均明显升高；依西美坦联合放射组能明显使Bax蛋白升高，Bcl-2蛋白降低，但放射与依西美坦的使用顺序差异无统计学意义。结论：依西美坦对MCF-7细胞具有放射增敏作用，可能与促进细胞凋亡有关，放射与依西美坦的使用顺序对效果无影响。

Effect of concurrent or sequential exemestane combined with radiation on radiosensitivity of MCF-7 cells

Background and purpose:Radiotherapy and endocrine therapy are both important parts of adjuvant therapy for breast cancer, yet few studies have been conducted focusing on the interaction between radiation and endocrine therapy. Up to now, no conclusion has been drawn on the timing sequence of adjuvant radiation and endocrine therapy, which is indeed crucial in clinical practice. This study intended primarily to investigate the effect of concurrent or sequential exemestane combined with radiation on radiosensitivity of MCF-7 cells and its possible mechanism,and further to provide rationale for optimal clinical treatment modality.Methods:MCF-7 cells were arranged into three trial groups: the radiation group, exemestane sequenced with radiation group and exemestane followed radiation group. Radiosensitivity was evaluated by clonogenic assay, cell proliferation was measured by MTT assay, the ability to induce cell apoptosis was evaluated by DAPI staining assay, the changes of Bcl-2 and Bax were detected by Western blot.Results:Sensitive enhancement ratios (SER) were 1.51 and 1.37 in the exemestane sequenced with radiation group and exemestane followed radiation group, respectively. Compared with the radiation group, the percentage of cellular proliferation inhibition and apoptosis increased obviously in the exemestane sequenced with radiation group and exemestane followed radiation group. Exemestane combined with radiation made the Bax protein increase obviously and the Bcl-2 protein lowered significantly.Conclusion:Exemestane can enhance the radiosensitivity of MCF-7 cells, whose mechanism might be relevant to the promotion of cellular apoptosis. However,the treatment sequence does not affect the outcome.