CMPK1蛋白与阿霉素引起的多药耐药的相关性研究

发布时间：2018-05-22 10:05

  本文选题：阿霉素 + IC　； 参考：《中国药理学通报》2017年06期

【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;IC_(50)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;CMPK1siRNA构建CMPK1蛋白低表达模型。结果 IC_(50)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(IC_(50)~(HEK293-CMPK1)/IC_(50)~(HEK293-Control)=0.15,P0.01),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(P0.05)。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(IC_(50)~(MCF7-siCMPK1)/IC_(50)~(MCF7-Control)=3.6,P0.01),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]:Objective to analyze the possible targets of adriamycin and to screen adriamycin-resistant proteins. Methods HEK239 cells were transfected with plasmids to construct a high expression protein model. The drug sensitivity of the cells was detected by RT-PCR. The expression of CMPK1 protein was detected by Western blot and the low expression model of CMPK1 protein was constructed by detecting the expression of CMPK1 protein. Results the results showed that the sensitivity of cells with high expression of CMPK1 protein to adriamycin increased the most. The expression level of CMPK1 protein was lower than that of MCF7(P0.05).MCF7 cells of breast cancer parent cell line MCF7 / ADM1, and the expression level of CMPK1 protein was lower than that of MCF7(P0.05).MCF7 cell line of breast cancer parent cell line MCF7 / ADM1, and the expression of CMPK1 protein was lower than that of MCF7(P0.05).MCF7 cell line of breast cancer parent cell line MCF7 / ADM1.The expression level of CMPK1 protein was lower than that of MCF7(P0.05).MCF7 cell line of breast cancer parent cell line MCF7 / ADM.The expression level of CMPK1 protein was lower than that of MCF7(P0.05).MCF7 cell line of breast cancer parent cell line. After the down-regulation of CMPK1 siRNA, The susceptibility to doxorubicin was decreased, and the susceptibility to paclitaxel and gemcitabine was also decreased. Conclusion CMPK1 is associated with multidrug resistance, and the expression of CMPK1 protein is positively correlated with drug sensitivity, suggesting that CMPK1 is a possible target for multidrug resistance therapy.
【作者单位】： 江南大学药学院药物设计与分子药理研究室;
【基金】：国家自然科学基金国际(地区)合作与交流项目(No81361168001) 江苏省临床医学科技专项(No BL2014019)
【分类号】：R96
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