| 陈宝安,郭晶晶,程坚,高峰,丁家华,许文林,沈惠玲,孙新臣,成红艳,高冲,孙耘玉,王骏,赵刚,宋慧慧,鲍文,李国宏,刘莉洁,陈文姬,王雪梅.环孢菌素A联合汉防己甲素逆转人白血病耐药细胞株K562/A02细胞多药耐药的分子生物学机制[J].,2008,(11):1010-1013 |
| 环孢菌素A联合汉防己甲素逆转人白血病耐药细胞株K562/A02细胞多药耐药的分子生物学机制 |
| Biomolecular Mechanisms of Cyclosporine A,Tetrandrine and Their Combination on the Reversion of Multidrug Resistance in Human Leukemia Cell Line |
| |
| DOI： |
| 中文关键词: 环孢菌素A 汉防己甲素 K562/A02细胞 多药耐药 P-糖蛋白 |
| 英文关键词:cyclosporine A tetrandrine K562/A02 cell multidrug resistance P-glycoprotein |
| 基金项目:国家自然科学基金资助项目(No.39970832);国家自然科学基金资助项目(No.30740062);江苏省科技计划资助项目(No.BS2004024);高等学校博士学科点专项科研基金(No.20070286042) |
|
| Hits: 1696 |
| Download times: 1 |
| 中文摘要: |
| 目的多药耐药(multidrug resistance,MDR)是导致肿瘤化疗失败的主要原因,本研究探讨环孢菌素A(cyclosporine A,CsA)及汉防己甲素(tetrandrine,Tet)联合应用对人白血病耐药细胞株K562/A02细胞MDR的逆转作用及其分子生物学机制。方法K562/A02细胞经CsA和Tet作用后,以流式细胞仪(FCM)检测细胞内柔红霉素(daunorubicin,DNR)浓度和P-糖蛋白(P-glycoprotein,P-gp)的表达,逆转录聚合酶链反应(reverse transcription polymerase chain reaction,RT-PCR)检测多药耐药基因(multidrug resistancegene,mdr1)mRNA表达水平。结果K562/A02细胞内DNR浓度为K562的19%,CsA(1mg/L)及Tet(0.1mg/L)单独及联合作用K562/A02细胞48h后细胞内DNR的浓度分别为K562的60%、65%、98%。K562和K562/A02细胞P-gp荧光强度分别为0.18%和96.51%,K562/A02细胞经CsA(1mg/L)和Tet(0.1mg/L)单独及联合处理后细胞P-gp荧光强度分别为75.32%,76.86%和48.61%。K562/A02细胞经过两药单独作用后耐药株mdr1-mRNA下调微弱,联合用药下调效果明显。结论环孢菌素A和汉防己甲素均可逆转白血病细胞的耐药,且两药联合作用逆转效果增强,具有协同作用。 |
| 英文摘要: |
| Objective Multidrug resistance(MDR)plays an important role in the failure of chemotherapy on malignant tumors.This study was to investigate the biomolecular mechanisms of cyclosporine A(CsA),tetrandrine(Tet)and their combination on multidrug resistance in cell line K562/A02.Methods K562/A02 cells were treated with CsA and(or)Tet.The intracellular daunorubicin(DNR)concentration and the expression of P-glycoprotein(P-gp)were observed by flow cytometry assay.The mRNA expression of mudtiding resistance gene(mdr1)was measured by fluorescent semi-quantitative reverse transcriptase polymerase chain reaction(RT-PCR).Results CsA and Tet(alone or combination)elevated the intracellular DNR concentration in K562/A02 cells(the fluorescence intensity of intracellular DNR in K562/A02 cells was 60%,65% and 98% respectively of that in K562 cells).The fluorescence intensity of P-gp in K562 and K562/A02 cells was 0.18% and 96.51%.The P-gp expression was down-regulated after treated with CsA,Tet and both(75.32%,76.86% and 48.61%);mdr1 mRNA was also down-regulated,and the effect of their combination was more obvious.Conclusion MDR can be partially reversed by CsA or Tet,the combination of both drugs shows a great synergistic reversal effect. |
| View Full Text View/Add Comment Download reader |
|
|
|
