[1]陈淑娴,叶向晖,王叙,等.CMPK1蛋白与阿霉素引起的多药耐药的相关性研究[J].中国药理学通报,2017,(06):788-792.[doi:10.3969/j.issn.1001-1978.2017.06.010]
 CHEN Shu-xian,YE Xiang-hui,WANG Xu,et al.Relationship between CMPK1 protein and ADM caused multidrug resistance[J].Chinese Pharmacological Bulletin,2017,(06):788-792.[doi:10.3969/j.issn.1001-1978.2017.06.010]
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CMPK1蛋白与阿霉素引起的多药耐药的相关性研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2017年06期
页码:
788-792
栏目:
论著
出版日期:
2017-06-15

文章信息/Info

Title:
Relationship between CMPK1 protein and ADM caused multidrug resistance
作者:
陈淑娴叶向晖王叙金坚
江南大学药学院 药物设计与分子药理研究室,江苏 无锡 214122
Author(s):
CHEN Shu-xianYE Xiang-hui WANG Xu JIN Jian
Laboratory of drug design and Molecular Pharmacology,School of Medicine and Pharmaceutics,Jiangnan University,Wuxi Jiangsu 214122,China
关键词:
阿霉素 IC50 药敏性 多药耐药 CMPK1 紫杉醇 吉西他滨
Keywords:
adriamycin IC50 drug sensitivity CMPK1 paclitaxel gemcitabine
分类号:
R329.24; R394.2; R737.902.2; R737.905.3; R979.1
DOI:
10.3969/j.issn.1001-1978.2017.06.010
文献标志码:
A
摘要:
目的 对阿霉素可能的作用靶点进行分析,筛选阿霉素耐药相关蛋白。方法 质粒转染HEK239细胞以构建蛋白高表达模型; IC50检测细胞的药敏性; RT-PCR检测细胞内基因的表达; Western blot检测CMPK1蛋白的表达; CMPK1 siRNA构建CMPK1蛋白低表达模型。结果 IC50检测结果表明高表达CMPK1蛋白的细胞对阿霉素的敏感性增加程度最大(IC50HEK293-CMPK1/IC50HEK293-Control=0.15,P<0.01),且阿霉素耐药细胞(MCF7/ADM)中CMPK1蛋白的表达低于乳腺癌亲本细胞MCF7(P<0.05)。MCF7细胞中,CMPK1蛋白表达水平经CMPK1 siRNA下调之后,对阿霉素的药敏性随之降低(IC50MCF7-siCMPK1/IC50MCF7-Control=3.6,P<0.01),且对紫杉醇、吉西他滨的药敏性也随之降低。结论 CMPK1与细胞的多药耐药相关,且CMPK1蛋白的表达与药敏性呈正相关,提示了CMPK1作为多药耐药治疗靶点的可能性。
Abstract:
Aim To assay the possible targets of adriamycin(ADM), screening ADM resistance related proteins. Methods The drug sensitivity of the cells was analyzed by IC50 assay; RT-PCR assay was used to detect the expression of genes in the cells; CMPK1 protein expression was tested by Western blot assay; the expression of CMPK1 in the cells was decreased by siRNA of CMPK1. Results Data from IC50 assay showed the sensitivity of cells transfected with CMPK1 was increased most(IC50 HEK293-CMPK /IC50 HEK293-Control=0.15, P<0.01), and the expression of CMPK1 protein in ADM resistant breast cells(MCF7/ADM)was lower than that in parent MCF7 cells(P<0.05). When the expression level of CMPK1 was decreased by CMPK1 siRNA, the sensitivity of MCF7 cells to ADM decreased(IC50 MCF7-siCMPK1/IC50MCF7-Control=3.6, P< 0.01), and the sensitivity of MCF7 cells to paclitaxel and gemcitabine also decreased. Conclusions CMPK1 was related to the multidrug resistance of cells, and the expression of CMPK1 was positively related to the sensitivity to drugs, which provides the possibility of CMPK1 as a target in the treatment of multidrug resistance.

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备注/Memo

备注/Memo:
收稿日期:2017-01-10,修回日期:2017-03-01 基金项目:国家自然科学基金国际(地区)合作与交流项目(No 81361168001); 江苏省临床医学科技专项(No BL 2014019) 作者简介:陈淑娴(1986-),女,博士,研究方向:药物设计与分子药理学,E-mail:csx.ss@163.com; 金 坚(1960-),男,博士,教授,博士生导师,研究方向:药物设计与分子药理学,通讯作者,E-mail:jinjian31@hotmail.com
更新日期/Last Update: 1900-01-01