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环孢菌素A逆转白血病多药耐药机制的实验研究
引用本文:赵春亭,杨纯正,杨天楹,邵晓枫,熊冬升,许元富,齐静.环孢菌素A逆转白血病多药耐药机制的实验研究[J].白血病.淋巴瘤,2001,10(2):68-70.
作者姓名:赵春亭  杨纯正  杨天楹  邵晓枫  熊冬升  许元富  齐静
作者单位:1. 山东青岛大学医学院附属医院
2. 中国医学科学院中国协和医科大学血液学研究所,天津,300020
摘    要:目的:研究环孢菌素A(CsA)持续作用7天后,K562/AO2细胞多药耐药性的变化及其变化机制,方法:细胞毒性试验采用MTTI地,细胞内柔红霉素(DNR)浓度用流式细胞术检测,多药耐药基因(mdrl)的表达水平用RT-PCR方法检测,结果:K562/AO2耐药性降低2.2倍,K562/AO2细胞内DNR浓度明显升高,mdrl表达降低,佛伯酯(TPA)可拮抗CsA升高细胞的DNR浓度的作用,结论:CsA可下调mdrl的表达和细胞内DNR浓度进而逆转MDR,其作用可能与CsA抑制蛋白激酶D(PKC)活性有关。

关 键 词:多药耐药  白血病  环孢菌素A  治疗
文章编号:1009-9921(2001)02-0068-03
修稿时间:2000年7月22日

EXPERIMENTAL STUDY ON REVERSAL MECHANISM OF MULTIDRUG RESISTANCE BY CYCLOSPORINE A
ZHAO Chun-ting,YANG Chun-zheng,YANG Tian-ying,et al Institute of Hematology,CAMS and PUMC.EXPERIMENTAL STUDY ON REVERSAL MECHANISM OF MULTIDRUG RESISTANCE BY CYCLOSPORINE A[J].Journal of Leukemia & Lymphoma,2001,10(2):68-70.
Authors:ZHAO Chun-ting  YANG Chun-zheng  YANG Tian-ying  Institute of Hematology  CAMS and PUMC
Abstract:Objective:To investigate the variation of multidrug resistance (MDR) in K562/AO2 cells after the sustaining affection on K562/AO2 cells by cyclosporine A.Methods:Cytotoxic effect was assayed by MTT method after K562/AO2 cells were cultured in CsA-containing medium for 7 days.Flow cytometry was used to mersured the intracellular daunorubicin concentration.The expression of MDR gene was analysied by RT-PCR method.Rusults:The sensitivity of to K562/AO2 cells to DNR increased by about 2 times with the increasing of intracellular DNR concentration which can be antagonized by phorbol ester (TPA) and the decreasing of mdr1 gene expression.Conclusion:CsA could reverse the MDR in K562/AO2 cells by down-regulation the expression of mdr1 gene and increasing the intracellular drug concentration.These might be contributed to it's inhibiting effect on protein kinase C(PKC) activity.
Keywords:Multidrug resistance  Leukemia  Cyclosporine A
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