中文摘要：

目的：探讨生理浓度（10^-9mol／L）褪黑素和药理浓度（10^-5mol／L）褪黑素对阿霉素抑制ER^＋乳腺癌细胞MCF-7作用影响及其机制。方法：1）应用四甲基偶氮唑蓝（MTT）法检测经不同浓度褪黑素孵育后阿霉素对MCF-7的抑制率和IC50变化。2）应用流式细胞学方法观察不同浓度褪黑素、阿霉素以及两药联用时对MCF-7凋亡的影响。3）应用Western blotting法检测不同浓度褪黑素、阿霉素单药和两药联用对MCF-7细胞p53和bcl-2蛋白表达的影响。结果：1）阿霉素对MCF-7乳腺癌细胞具有明显的抑制作用，且成剂量时间依赖性。IC50值为0．62±0．071μg／ml，经生理浓度和药理浓度褪黑素孵育后IC50值分别降为0．59±0．09μg／ml和0．42±0．02μg／ml，前者与孵育前相比未见统计学差异（P〉0．05），后者相比差异显著（P〈0．01）。2）流式细胞学检测结果显示：阿霉素对MCF-7细胞具有凋亡促进作用，随浓度增高凋亡率未见增加（P〉0．05）。生理浓度褪黑素联合阿霉素与相应浓度的阿霉素单药相比，凋亡率未见明显增加（P〉0．05）。药理浓度褪黑素联合阿霉素与相应浓度阿霉素单药比较，凋亡率明显增加（P〈0．05），联合组随着阿霉素浓度增加凋亡率并未见明显变化（P〉0．05）。3）MCF-7乳腺癌细胞株中呈p53蛋白低袁达、bcl-2蛋白高表达。生理浓度褪黑素即可显著增高MCF-7细胞p53蛋白并降低bcl-2蛋白表达，并有剂量依赖性（P〈0．01）。药理浓度褪黑素联合不同浓度阿霉素对两个蛋白表达未见显著性差异（P〉0.05）；阿霉素对两种蛋白表达未见明显影响（P〉0．05）。结论：1）生理浓度褪黑素（10^-9mol／L）对阿霉素的抗癌作用未见明显影响，药理浓度（10^-5mol/L）以上褪黑素表现出对阿霉素明显的增敏作用。2）阿霉素较低浓度时，凋亡促进作用可能是褪黑素对其增敏机制的?

英文摘要：

Objective： To investigate the sensitization of physiological （10^-9mol/L） and pharmacological （10^-5mol/L） concentrations of melatonin on cell line MCF-7 for adriamycin and its mechanism. Methods： （1） MTT was applied to test the changes in inhibition ratio and IC50 of cell line MCF-7 for adriamycin before and after incubation with melatonin. （2） Flow cytometry was used to observe the effect of different concentrations of melatonin, adriamycin and melatonin plus adriamycin on cell apoptosis. （3） Western blot was employed to determine the expression of p53 and bcl-2 in MCF-7 cells incubated with melatonin, adriamycin and melatonin plus adriamycin. Results： （1） MTT method showed that adriamycin had inhibitive effect on the growth of MCF-7 cells in a dose- and time-dependent manner. The IC50 of cell line MCF-7 for adriamycin before treatment with melatonin was 0.62±0.07ug/mL （P〉0.05）. The IC50 of cell line MCF-7 for adriamycin incubated with physiological and pharmacological concentrations of melatonin was 0.59±0.09ug/mL and 0.42±0.02ug/mL, respectively, with a significant difference （P〈0.01）. （2） Flow cytometry method showed that adriamycin could promote apoptosis of MCF-7, and no changes in the apoptosis index were observed as the concentration of melatonin was changed （P〉0.05）. With the same concentration of adriamycin, the apoptosis index of cells treated with physiological concentration of melatonin plus adriamycin was not changed （P〉0.05）, but the apoptosis index of cells treated with pharmacological concentrations of melatonin plus adriamycin was increased significantly. The concentration of adriamycin had no effect on the apoptosis index. （3） Western blot showed that P53 protein was expressed at a lower level and bcl-2 protein was highly expressed. Physiological concentrations of melatonin increased the expression of p53 and decreased bcl-2 expression in a dose dependent manner. The concentration of adriamycin had no effect on the expression of