中国临床药理学与治疗学2017，Vol.22Issue(5)：512-517,6.
姜黄素通过调控组蛋白乙酰化修饰上调乳腺癌MCF-7和MCF-7/DOX细胞中MDR1表达
Curcumin increases MDR1 expression in breast cancer MCF-7 and MCF-7/DOX cells through regulating histone acetylation
摘要
Abstract
AIM:To study the effect of curcumin on historie acetylation and the expression level of MDR1 (multidrug resistance protein 1) in breast cancer cells MCF-7 and MCF-7/DOX.METHODS:The effect of curcumin on the growth proliferation and sensitivities of doxorubicin against MCF-7 and MCF-7/DOX cells were evaluated by CCK-8 (Cell Counting Kit-8) assay.Real-time PCR and Western blot assays were used to detect the expression levels of MDR1 in MCF-7 and MCF-7/DOX cells.The acetylation levels of MDR1 promoter region related histone H3,H4 were detected by chromatin immunoprecipitation assay.RESULTS:Curcumin inhibited the growth of MCF-7 and MCF-7/ DOX cells with the IC50 values of 22.03 μmol/L and 27.46 μmol/L,respectively.The doxorubicin sensitivity of MCF-7 and MCF-7/DOX cells were significantly increased after the treatment of 10 μmol/L curcumin for 72 h,and the values of IC50 were decreased by 57.14％ and 54.52％ (P ＜ 0.05),respectively.After curcumin treatment,MDR1 mRNA levels were (32.90 ± 0.96) and (5.70 ± 0.55) folds increased in MCF-7 and MCF-7/DOX cells (P ＜ 0.05),respectively;MDR1 protein levels were (2.26 ±0.18) and (2.90 ± 0.21) folds increased in MCF-7 and MCF-7/DOX cells (P ＜ 0.05),respectively.The MDR1 promoter region related levels of histone H3 and H4 acetylation in MCF-7 and MCF-7/DOX cells were significantly induced by curcumin (P ＜ 0.05).CONCLUSION:Curcumin enhances the doxorubicin sensitivities in MCF-7 and MCF-7/DOX cells.Moreover,it induces the MDR1 expression via increasing the MDR1 promoter region related levels of histone H3 and H4 acetylation.关键词
姜黄素/MCF-7/MCF-7/DOX/多药耐药基因1/乙酰化Key words
curcumin/MCF-7/MCF-7/DOX/multidrug resistance protein 1/acetylation分类
医药卫生引用本文复制引用
李絮,代谊,黄家凤,温纯洁,邹镇,吴兰香,王果,周宏灏..姜黄素通过调控组蛋白乙酰化修饰上调乳腺癌MCF-7和MCF-7/DOX细胞中MDR1表达[J].中国临床药理学与治疗学,2017,22(5):512-517,6.基金项目
国家自然科学基金(81473284,81102511) （81473284,81102511）
重庆市自然科学基金cstc2011jjA10004) （）
重庆市医学科研计划项目(2013-2-150) （2013-2-150）
重庆市渝中区科技计划项目(0130127) （0130127）
