中国药理学与毒理学杂志Issue(2)：247-252,6.DOI:10.3867/j.issn.1000-3002.2015.02.010
丙戊酸对乳腺癌细胞放射敏感性的影响
Effect of vaIproic acid on radiosensitivity to breast cancer ceIIs
摘要
Abstract
OBJECTIVE To study the effect of valproic acid ( VPA) on radiosensitivity to MCF7 breast cancer cells. METHODS MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively, irradiated with 8 Gy lR, and at 6 h post-lR, the γ-H2 AX foci formation in MCF7 cells was tested by immunofluorescence assay. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 72 h, irradiated with 4 Gy lR, and at 48 h post-lR, the cell survival rate was detected by MTT assay. MCF7 cells were pretreated with VPA 0.5 mmol.L-1 for 24 h, and then irradiated according to the amount of cells: 2 Gy (500 and 1000 cells per plate), 4 Gy (2000 and 4000 cells per plate), 6 Gy (8000 and 16000 cells per plate), and the cloning efficiency was calculated. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively and the cell cycle profile was analyzed via flow cytometry. RESULTS After treatment with VPA alone for 24 h, MCF7 cells showed a significant increase in the amount of γ-H2 AX foci formation ( P < 0. 01). lt was also found that VPA increased lR-induced γ-H2 AX foci formation, which obviously prolonged the pretreatment time of VPA(P<0.01) in a time-dependent manner(r=0.98, P<0.05). VPA 0.5 and 1 mmol.L-1 had the same effect on γ-H2 AX foci formation. Furthermore, VPA was able to cause a significant decrease in lR-induced clonogenic survival but an increase in lR-induced cytotoxicity by MTT assay. Also, VPA alone decreased the plating efficiency of MCF7 cells. However, the cycle profile of MCF7 cells treated with both VPA 0.5 and 1 mmol.L-1 was not changed. CONCLUSION Without affecting the cell cycle profile, both the safe and critical dose of VPA used in clinical epilepsy treatment can significantly increase the accumulation of DNA double strand breaks in the cells and sensitize the cells to lR treatment, suggesting that VPA can induce radio-sensitization of breast cancer cells.关键词
丙戊酸/乳腺癌/DNA 损伤/放射增敏/细胞周期Key words
valproic acid/breast cancer/DNA damage/radiosensitivity/cell cycle分类
医药卫生引用本文复制引用
赵锡鹏,罗月,董超,张凤梅,凤志慧..丙戊酸对乳腺癌细胞放射敏感性的影响[J].中国药理学与毒理学杂志,2015,(2):247-252,6.基金项目
国家自然科学基金(81172527)国家自然科学基金项目(81472800)山东省科技发展计划(2013GGE27052)@@@@The project supported by National Natural Science Foundation of China(81172527) National Natural Science Foundation of China (81472800) and Science and Technology Program of Shandong Province (2013GGE27052) （81172527）
