本文選題：阿霉素 + IC　； 參考：《中國(guó)藥理學(xué)通報(bào)》2017年06期

【摘要】：目的對(duì)阿霉素可能的作用靶點(diǎn)進(jìn)行分析,篩選阿霉素耐藥相關(guān)蛋白。方法質(zhì)粒轉(zhuǎn)染HEK239細(xì)胞以構(gòu)建蛋白高表達(dá)模型;IC_(50)檢測(cè)細(xì)胞的藥敏性;RT-PCR檢測(cè)細(xì)胞內(nèi)基因的表達(dá);Western blot檢測(cè)CMPK1蛋白的表達(dá);CMPK1siRNA構(gòu)建CMPK1蛋白低表達(dá)模型。結(jié)果 IC_(50)檢測(cè)結(jié)果表明高表達(dá)CMPK1蛋白的細(xì)胞對(duì)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),且阿霉素耐藥細(xì)胞(MCF7/ADM)中CMPK1蛋白的表達(dá)低于乳腺癌親本細(xì)胞MCF7(P0.05)。MCF7細(xì)胞中,CMPK1蛋白表達(dá)水平經(jīng)CMPK1 siRNA下調(diào)之后,對(duì)阿霉素的藥敏性隨之降低(IC_(50)~(MCF7-siCMPK1)/IC_(50)~(MCF7-Control)=3.6,P0.01),且對(duì)紫杉醇、吉西他濱的藥敏性也隨之降低。結(jié)論 CMPK1與細(xì)胞的多藥耐藥相關(guān),且CMPK1蛋白的表達(dá)與藥敏性呈正相關(guān),提示了CMPK1作為多藥耐藥治療靶點(diǎn)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.
【作者單位】： 江南大學(xué)藥學(xué)院藥物設(shè)計(jì)與分子藥理研究室;
【基金】：國(guó)家自然科學(xué)基金國(guó)際(地區(qū))合作與交流項(xiàng)目(No81361168001) 江蘇省臨床醫(yī)學(xué)科技專項(xiàng)(No BL2014019)
【分類號(hào)】：R96
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本文編號(hào)：1921617