HSP27高表达与人白血病多药耐药细胞K562/VCR的关系

背景与目的:白血病细胞多药耐药(multidrug resistance,MDR)是白血病化疗失败的常见原因,虽然已有研究揭示了一些肿瘤MDR机制,但目前仍然不能完全解释MDR现象。本文旨在应用蛋白质组学方法筛选白血病耐药相关蛋白,并研究其与白血病MDR的关系,为进一步阐明白血病MDR发生的分子机制提供理论依据。方法:二维聚丙烯酰胺凝胶电泳(two-dimensional electrophoresis,2-DE)技术分离白血病细胞K562和人白血病耐药细胞K562/VCR的总蛋白,用基质辅助激光解吸电离飞行时间质谱(matrix assisted laser desorption/ionization-time offlight-mass spectrometry,MALDI-TOF-MS)对差异表达的蛋白质点进行鉴定。应用反义核酸技术将分离鉴定差异表达蛋白的反义核酸转染至耐药细胞,Western blot检测转染后差异蛋白的表达情况,MTT法检测转染后细胞存活率,流式细胞仪检测转染后细胞凋亡率。结果:在K562/VCR细胞与K562细胞中鉴定出一差异表达蛋白点,并用质谱分析证实其为热休克蛋白27(heat shock protein27,HSP27)。用HSP27反义核酸转染K562/VCR细胞,在不同浓度长春新碱作用下,HSP27反义核酸转染的K562/VCR细胞的存活率较对照错义核酸转染组明显降低(P<0.05),流式细胞仪显示细胞凋亡率为16.37%,明显高于对照组(P<0.05)。结论:HSP27在K562/VCR细胞中高表达,其表达抑制后,K562/VCR细胞对长春新碱的敏感性增强。     

差异凝胶电泳筛选人骨肉瘤细胞多药耐药相关蛋白

摘 要 目的: 应用差异凝胶电泳分析骨肉瘤多药耐药细胞株与亲本细胞株蛋白质表达的差别，筛查骨肉瘤细胞多药耐药相关蛋白。方法：以小剂量多柔比星（doxorubicin, DXR）诱导人骨肉瘤细胞株MG63，建立骨肉瘤多药耐药细胞株MG63/DXR100。以差异凝胶电泳分离两组细胞中的全部蛋白质，应用图像扫描和DeCyder软件分析差异（表达增加或减少>30%）表达的蛋白质点，对其进行质谱鉴定，并在Mascot 数据库中检索。结果：共检测到明显差异表达的蛋白质点30个，选择其中18个点进行质谱鉴定，有5个蛋白质点鉴定成功，它们分别是与肿瘤细胞转移相关的基质金属蛋白酶1（matrix metalloproteinases 1, MMP1）、具有解毒功能的乙醇脱氢酶6（alcohol dehydrogenase 6, ADH6）、属于抑癌基因的FERM域结合蛋白3（FERM domain containing protein 3, FRMD3），以及两个分别由128和300个氨基酸残基构成的未知蛋白。MMP1、ADH6和2种未知蛋白在耐药细胞表达显著高于非耐药细胞组，而FRMD3表达显著显著低于非耐药细胞。结论：通过差异凝胶电泳筛查到，MMP1、ADH6、FRMD3 及2种未知蛋白质在骨肉瘤细胞的多药耐药细胞和非耐药细胞中差异表达，它们可能参与骨肉瘤细胞的多药耐药机制。     

应用蛋白质芯片检测多药耐药蛋白表达水平

目的探讨蛋白质芯片在检测白血病细胞多药耐药(MDR)蛋白表达中的价值。方法以人红白血病细胞系K562及其耐药细胞系K562/A02为实验研究对象。将3种耐药蛋白P糖蛋白(P-gP)、多药耐药相关蛋白(MRP1)和乳腺癌耐药蛋白(BCRP)相应的单克隆抗体固定在玻片上形成微阵列,细胞直接与固定在芯片上的耐药抗体阵列反应,电荷耦合器件(CCD)检测反应结果,并与流式细胞术测定的结果进行比较分析。结果在K562细胞中,蛋白质芯片检测到P-gP和BCRP表达率低,MRP1有较高水平的表达;在K562/A02细胞中,P-gP和MRP1均有高水平表达,BCRP表达率低。流式细胞术结果显示,K562细胞P-gP、MRP1和BCRP表达率分别为5.98%±2.19%、95.80%±3.98%和1.03%±0.45%;K562/A02细胞P-gP、MRP1和BCRP表达率分别为92.67%±1.80%、97.18%±1.02%和3.98%±0.37%。经统计学分析,两种方法结果一致(Ρ>0.05)。结论利用蛋白质芯片检测MDR蛋白结果可靠,具有高通量、低成本、制备简单、测定快速的优点。     

氯丙嗪对耐药细胞系K_(562)/AO_2多药耐药逆转作用的研究

目的 :研究氯丙嗪对耐药细胞系K562 /AO2 多药耐药逆转作用。方法 :应用免疫组化观察K562 /AO2 细胞系的耐药蛋白表达情况 ,用MTT法测定不同浓度的氯丙嗪对K562 /AO2 细胞系耐药逆转作用 ,用流式细胞术测定不同浓度的氯丙嗪与K562 /AO2 细胞作用后细胞内罗丹明的蓄积情况 ,用半定量RT PCR法测定氯丙嗪对K562 /AO2 细胞多药耐药基因 (mdr 1)mRNA表达的影响。结果 :K562 /AO2 细胞不但P gp表达阳性 ,而且肺耐药相关蛋白 (lungresistanceelatedprotein ,LRP)表达也阳性 ;氯丙嗪能增强多柔比星对K562 /AO2 细胞的杀伤作用 (单用ADM组、氯丙嗪 0 75 μg/mL ADM组、氯丙嗪 1 5μg/mL ADM组和氯丙嗪 3 μg/mL ADM组对K562 /AO2 的抑制率分别为 5 2 %、 2 5 9%、3 9 1%和 74 8% ) ;增加K562 /AO2 细胞内罗丹明的蓄积 (对照组、氯丙嗪 0 75 μg/mL组、氯丙嗪1 5 μg/mL组和氯丙嗪 3μg/mL组细胞内的荧光强度的均值分别为 1 87、 10 2 8、 48 75和65 63 ) ;对K562 /AO2 细胞mdr 1mRNA表达无明显影响 (对照组mdr 1和 β actin的面积比为0 41,氯丙嗪组为 0 42 )。结论 :氯丙嗪对K562 /AO2 细胞的耐药有较强的逆转作用 ,并呈剂量依赖关系     

斑蝥酸钠逆转K562/AO2细胞多药耐药的机制初探

目的 观察斑蝥酸钠(SCA)对多药耐药的白血病细胞(K562/AO2)细胞是否有逆转作用,并初步探讨其逆转机制.方法 应用 MTT测定多柔比星(阿霉素,ADM)对K562/AO2细胞的半数抑制浓度(IC50);应用逆转录聚合酶链式反应(RT-PCR)检测K562、K562/AO2细胞表达mdr1基因水平;用流式细胞术(FCM)检测其P-gp蛋白表达的水平.结果 MTT结果显示,无毒剂量的SCA与ADM联合应用比单纯加ADM(同等剂量)对K562/AO2细胞的IC50降低了1.51倍;耐药细胞(K562/AO2)经SCA处理后mdr1基因与P-gp蛋白表达均下降(P＜0.05).结论 SCA对K562/AO2有一定的逆转作用,其机制可能与下调mdr1基因和P-gp蛋白表达有关.     

氯丙嗪对耐药细胞系K562/AO2多药耐药逆转作用的研究

目的研究氯丙嗪对耐药细胞系K562/AO2多药耐药逆转作用.方法应用免疫组化观察K562/AO2细胞系的耐药蛋白表达情况,用MTT法测定不同浓度的氯丙嗪对K562/AO2细胞系耐药逆转作用,用流式细胞术测定不同浓度的氯丙嗪与K562/AO2细胞作用后细胞内罗丹明的蓄积情况,用半定量RT-PCR法测定氯丙嗪对K562/AO2细胞多药耐药基因(mdr-1)mRNA表达的影响.结果K562/AO2细胞不但P-gp表达阳性,而且肺耐药相关蛋白(lung resistanceelatedprotein,LRP)表达也阳性;氯丙嗪能增强多柔比星对K562/AO2细胞的杀伤作用(单用ADM组、氯丙嗪0.75 μg/mL+ADM组、氯丙嗪1.5μg/m L+ADM组和氯丙嗪3μg/mL+ADM组对K562/AO2的抑制率分别为5.2%、25.9%、39.1%和74.8%)增加K562/AO2细胞内罗丹明的蓄积(对照组、氯丙嗪0.75 μg/mL组、氯丙嗪1.5 μg/mL组和氯丙嗪3μg/mL组细胞内的荧光强度的均值分别为1.87、10.28、48.75和65.63)对K562/AO2细胞mdr-1 mRNA表达无明显影响(对照组mdr-1和β-actin的面积比为0.41,氯丙嗪组为0.42).结论氯丙嗪对K562/AO2细胞的耐药有较强的逆转作用,并呈剂量依赖关系.     

胃癌细胞耐药相关蛋白质分子的差异展示

目的 寻找新的胃癌细胞耐药相关蛋白质分子,阐明肿瘤耐药的新机制。方法 以胃癌细胞SGC7901和长春新碱诱导的耐药胃癌细胞SGC7901／VCR为研究对象,用固相化pH梯度等电聚焦的二维聚丙烯酰胺凝胶电泳技术展示并比较两种细胞表达的所有蛋白质,凝胶银染法显示耐药与非耐药细胞差异表达的蛋白质分子。结果 在两张银染的凝胶蛋白质图谱上,均有680个可辨识的蛋白质点,绝大多数蛋白点在位置、形状和密度上是一致的。在耐药细胞蛋白质二维电泳图谱中,发现有30个明显差异的蛋白点,并初步确定了其等电点和分子量。其中3个蛋白点表达量很高,但在非耐药细胞中未出现;6个蛋白点丰度明显上调;19个蛋白点丰度明显下调;2个蛋白点在耐药细胞中未出现,但在非耐药细胞中高表达。结论 胃癌耐药细胞中差异表达的蛋白质分子可能与其长春新碱耐药机制相关。     

维甲酸耐药细胞与敏感细胞的差异表达蛋白分析

背景与目的:维甲酸耐药机制有待进一步的深入研究。蛋白质组学以所有蛋白质为研究对象,从细胞水平及整体水平研究蛋白质的组成及其变化规律。本实验应用蛋白组学技术整体比较维甲酸耐药细胞与敏感细胞蛋白表达谱,筛选差异表达蛋白,以期获得维甲酸耐药相关蛋白。方法:提取维甲酸耐药细胞株MR2及维甲酸敏感细胞株NB4的总蛋白,通过双向凝胶电泳分离,获得二者高质量的蛋白表达谱,经PDQuestv7.1软件比较分析,筛选出二者间差异表达的蛋白质点,通过质谱仪鉴定表达差异的蛋白。结果:获得了分辨率高、重复性好的APL细胞的双向电泳图谱。PDQuestv7.1软件分析结果表明,MR2细胞及NB4细胞的pH4～7双向凝胶电泳所展示的蛋白点分别有(890±45)个和(912±56)个。二者间有57个差异显著的蛋白点,其中23个在MR2细胞中上调,34个下调。经质谱鉴定了10个蛋白,鉴定成功率达70%,鉴定的蛋白涉及癌蛋白、细胞周期调控和信号转导相关蛋白质。结论:应用双向凝胶电泳技术整体展示了维甲酸耐药细胞株MR2及敏感细胞株NB4的蛋白表达谱,并分析、鉴定、筛选出与维甲酸耐药相关的差异表达蛋白,为进一步从多因素角度研究认识维甲酸耐药机制提供了新的线索。     

卵巢癌铂类耐药细胞株与敏感株间差异蛋白的筛选

目的:筛选卵巢癌铂类耐药细胞和敏感细胞间的差异蛋白质.方法:提取卵巢癌耐卡铂细胞SKOV3/CB和亲本细胞SKOV3的总蛋白,用二维液相色谱技术(ProtemeLabTM PF-2D)分离、筛选差异蛋白,用电喷雾离子化串联质谱(ESI-MS/MS)分析鉴定蛋白质.结果:共分离筛选出差异蛋白54个,其中SKOV3/CB表达上调的34个,SKOV3表达上调的20个.初步鉴定出5个SKOV3/CB表达上调的差异蛋白,即硫氧还原蛋白(thioredoxin,Trx)、Myosin regulatory light polypeptide 9(MYL9)、AX887247 NID、stanniocalcin homolog、human regulator ofG-protein signaling 5(RGS-5).这些蛋白涉及氧化还原、凋亡调控、甲基化及信号传导等多方面.结论:卵巢癌铂类耐药细胞和敏感细胞间存在蛋白表达差异,这些差异蛋白可能通过多种机制介导了卵巢癌对铂类的耐药.     

氯丙嗪对耐药细胞系K562／AO2多药耐药逆转作用的研究

目的：研究氯丙嗪对耐药细胞系K562/AO2多药耐药逆转作用。方法：应用免疫组化观察K562／AO2细胞系的耐药蛋白表达情况，用MTT法测定不同浓度的氯丙嗪对K562/AO2细胞系耐药逆转作用，用流式细胞术测定不同浓度的氯丙嗪与K562／AO2细胞作用后细胞内罗丹明的蓄积情况，用半定量RT—PCR法测定氯丙嗪对K562／AO2细胞多药耐药基因(mdr-1)mRNA表达的影响。结果：K562／AO2细胞不但P-gP表达阳性，而且肺耐药相关蛋白(lung resistanceelated protein．LRP)表达也阳性；氯丙嗪能增强多柔比星对K562／AO2细胞的杀伤作用(单用ADM组、氯丙嗪0．75μg／mL+ADM组、氯丙嗪1．5μg／mL+ADM组和氯丙嗪3μg／mL+ADM组对K562／AO2的抑制率分别为5．2％、25．9％、39．1％和74．8％)；增加K562／AO2细胞内罗丹明的蓄积(对照组、氯丙嗪0．75μg／mL组、氯丙嗪1．5μg/mL组和氯丙嗪3μg／mL组细胞内的荧光强度的均值分别为1．87、10．28、48．75和65．63)；对K562／AO2细胞mdr-1 mRNA表达无明显影响(对照组mdr-1和β-actin的面积比为0．41，氯丙嗪组为0．42)。结论：氯丙嗪对K562／AO2细胞的耐药有较强的逆转作用，并呈剂量依赖关系。     

二甲亚砜对K562/ADM耐药细胞株耐药性的逆转作用

目的：研究二甲亚砜对K562／ADM耐药细胞的逆转作用。方法：通过加入二甲亚砜后耐药细胞的生长情况，逆转倍数的计算，细胞内过氧化物染色的阳性程度以及电镜下观察耐药细胞诱导前后的变化。结果：二甲亚砜诱导K562／ADM耐药细胞前后生长情况有显著差异且逆转借故为4．0，Pox染色阳性程度明显递增，电镜下可观察诱导后K562／ADM耐药细胞有向成熟分化趋势。结论：二甲亚砜对逆转K562／ADM的耐药性是有益的。     

Establishment of K562/ADM/VER cell subline resistant to verapamil and its resistant mechanism

Failure of chemotherapy for cancer results mainly from resistance to chemotherapy. Tens kind of reversors have been found to reverse resistance of tumor cell to anticancer drugs in vitro. Interestingly, tumor cells were observed to develop resistance to the resistance reversors recently. Multidrug resistant cells, EMT16 have been reported to produce resistance to verapamil (VER), a resistance reversor, from Reeve JG, et al.[1]. However, this fact has not been fully paid attention with no r…     

环腺苷酸对人白血病多药耐药 K562/ADM 细胞的诱导分化作用

目的：研究环腺苷酸（cyclic adenosine monophosphate,cAMP)对人白血病多药耐药K562／ADM细胞的诱导分化作用。方法：K562／ADM细胞经0.25-2.0mmol/L cAMP处理后,MTT法检测细胞增殖活性,流式细胞术（flow cytometry,FCM)检测细胞周期和P－糖蛋白（P－glycoprotein,P-gp)的表达,免疫细胞化学法检测细胞周期蛋白cyclin D1和转录因子E2F的表达;同时观察细胞形态学变化和血红蛋白合成功能。结果：cAMP呈浓度和时间依赖性地抑制K562／ADM细胞的增殖（P＜0．01）,细胞形态学上出现红系细胞的形态特征;被诱导的细胞能够合成血红蛋白、cyclinD1和E2F的表达减低。cAMP(0.25mmol/L和1.0mmol/L)诱导24h,多数细胞被阻滞在G1期,S期和G2＋M期细胞显著降低,诱导72h后K562／ADM细胞P－gp表达的阳性率无明显变化（99．8％－99．9％）,但P－gp的表达量显著增加,平均荧光强度分别增高1．24倍和1．28倍。结论：K562／ADM细胞仍保留了分化成熟的潜能,可被cAMP诱导向正常血细胞分化,但在分化诱导过程中,化学诱导剂可导致耐药细胞发生P－gp的应激性表达增强而可能阻抑后续的化学治疗,或对诱导剂产生耐受性。     

硫化砷对K_(562)/ADM细胞HSP70蛋白表达的影响

目的 :探讨硫化砷 (As2 S2 )对K5 6 2 及其耐药细胞株K5 6 2 ADM细胞膜HSP70蛋白表达的影响。方法 :采用流式细胞仪 (FCM)测定K5 6 2 和耐药细胞K5 6 2 ADM细胞膜HSP70蛋白表达及细胞凋亡 ,利用RT PCR方法检测HSP70的mRNA水平。结果 :硫化砷能增加细胞膜HSP70蛋白表达 ,且与时间及浓度成正相关 ,而在mRNA水平上仍有较高的表达。K5 6 2 ADM细胞膜HSP70蛋白表达和细胞凋亡率均高于K5 6 2 细胞。结论 :硫化砷能增加细胞膜HSP70蛋白表达 ,且这种改变可能对细胞凋亡率产生一定影响     

Decitabine (5-Aza-2'-deoxycytidine) decreased DNA methylation and expression of MDR-1 gene in K562/ADM cells.

Multidrug resistance (MDR) is a major problem in patients with hematological malignancies. Although drug-resistance is known to be induced by the expression of P-glycoprotein (P-gp) encoded by the MDR-1 gene, little is known about the mechanisms regulating this gene. Herein, we studied the DNA methylation patterns at the enhancer and repressor binding sites of the MDR-1 gene using the human erythroleukemia cell line K562 and its multidrug resistant derivative K562/ADM (adriamycin). Direct DNA sequence analysis demonstrated methylation to be present at the repressor site (minus 110 GC-box) of the MDR-1 gene in K562/ADM cells, but not in parental K562 cells. Methylation-specific PCR (MSP) analysis yielded similar results. Treatment of K562/ADM cells with 5-Aza-2'-deoxycytidine (decitabine; DAC), an inhibitor of DNA methyltransferase, caused demethylation of the repressor binding site of MDR-1 gene, as assessed by MSP, and also decreased P-gp expression, as assessed by flow cytometric and Northern blot analysis. Although it is generally accepted that DAC upregulates gene expression by demethylating the activator binding sites, our present results suggest that DAC induces down-regulation of P-gp expression as a result of demethylation at the repressor binding site in K562/ADM cells. In this regard, methylation-dependent regulation of the MDR-1 gene in K562/ADM cells is unique.     

Mechanism of cytotoxic effects of taxotere in the K562 human premyelocytic leukemia line

Background Taxotere, a semisynthetic derivative of Taxol, is known to possess cytotoxic effects on various animal cells. Methods To better understand the precise mechanism of this drug action, the human promyelocytic leukemia cell line, K562, and its adriamycin and vincristine resistant sublines, respectively termed K562/ADM and K562/VCR, were used as targets. Results The IC₅₀ for taxotere was almost equal to that for VCR. Due to cross-resistance in the K562/ADM cells, the IC₅₀ value was 42.3 times greater with taxotere, although it was still lower than with ADM and VCR. A much lower cross-resistance was noted with the K562/VCR cells. Assessment of MDR-1 mRNA indicated that expression of the multidrug resistance gene product p-glycoprotein in the cell membrane was partly responsible for the resistance. K562 cells treated with taxotere accumulated in G₂M of the cell cycle, and morphologically, cells in metaphase were found to be remarkably increased. This indicates inhibition of mitosis. Unlike vincristine or vinblastine, taxotere enhanced the assembly of tubulin into microtubules in the absence of guanosine triphosphate (GTP). Moreover, microtubule disassembly was inhibited even in the presence of calcium ions. Conclusion These results suggest that the tubulin equilibrium was shifted towards formation and away from degradation of microtubules that lead to metaphase arrest and eventual cell death. Syntheses of DNA, RNA and protein were not inhibited, and topoisomerases I and II were unaffected. Thus taxotere is an analogue of Taxol, showing a similar mechanism of cytotoxic effect to Taxol on the human K562 leukemia cell line as well as on rodent tumor cell lines.     

Characteristics of resistance to adriamycin in human myelogenous leukemia K562 resistant to adriamycin and in isolated clones

An adriamycin (ADM)-resistant variant (K562/ADM) of human myelogenous leukemia K562 was established. K562/ADM was stable for 2 months in medium without ADM, and was 130-fold more resistant to ADM as compared to the parent K562. Twenty clones were isolated from K562/ADM by the limiting dilution technique. Five clones with different ADM sensitivity were selected and characterized further. The extent of clonal resistance to ADM was parallel to the extent of resistance to vincristine (VCR), except for one clone, KA-15. The majority of clones, including K562/ADM, accumulated far smaller amounts of daunomycin (DAU) or VCR as compared to the parent K562. However, a highly resistant clone did not necessarily accumulate less DAU in the cells, indicating that the mechanism of ADM resistance cannot be explained solely by a defect of ADM accumulation. All clones rapidly transported DAU and VCR from the cells. K562/ADM expressed on the cell surface three distinct glycoproteins with molecular weights of 180,000, 83,000 and 65,000 daltons. No change was detected in the actin and tubulin contents of K562 and clones. K562/ADM and its clones expressed double minute chromosomes and contained homogeneously staining regions in the chromosomes.     

潘生丁,凡拉帕米对逆转K562／ADM耐药性的研究

本研究结果提示:潘生丁、凡拉帕米均有增强ADM和VCR对K562和K562/ADM的作用,在ADM为0.01μg/ml时,对K562的抑制率为35.9％,当同时含有潘生丁6.25μg/ml～50.0μg/ml或凡拉帕米1.8μg/ml～14.4μg/ml时,使细胞的抑制率可分别再提高20.8％～34.50％和7.7％～29.5％,而对K562/ADM,潘生丁和凡拉帕米分别使细胞抑制率提高21.6％～70.9％和40.3％～61.1％。在VCR为0.1μg/ml时,对K562的抑制率为58.4％,当含有潘生丁或凡拉帕米时,抑制率可分别提高19.1％～24.9％和18.7％～22.6％,而对K562/ADM,在VCR8.0μg/ml时,抑制率为18.8％,当含有潘生丁或凡拉帕米时,抑制率可分别提高32.5％～45.1％和23.8％～35.4％。从上述结果可看出,潘生丁或凡拉帕米在逆转K562/ADM的耐药性是有益的。     

雷公藤红素逆转K562/A02细胞多药耐药的实验研究

目的探讨雷公藤红素逆转人慢性粒细胞白血病红白血病急变细胞株K562/A02多药耐药的效果。方法采用CCK-8法测定细胞的药敏性及耐药逆转性,应用流式细胞术检测细胞内ADM浓度、P-gp蛋白表达。结果雷公藤红素对K562/A02、K562的半数抑制率浓度（IC50）分别为（295.58±23.288）μmol/L、（411.59±26.551）μmol/L。K562/A02细胞对ADM的耐药性是K562细胞的79.78倍。细胞毒剂量的雷公藤红素作用后,ADM对K562/A02细胞的IC50显著下降（P〈0.05）,逆转倍数为117.860倍。细胞毒剂量（IC50）和非细胞毒剂量（IC10）的雷公藤红素处理后的K562/A02细胞内的ADM浓度显著增加（P〈0.05）,增加倍数分别为1.537倍和1.102倍。雷公藤红素能明显下调K562/A02细胞的P-gp表达。结论雷公藤红素对逆转K562/A02细胞的耐药性有一定的作用,其机制可能与下调P-gp表达有关。     

Anti-proliferative effect of the abl tyrosine kinase inhibitor STI571 on the P-glycoprotein positive K562/ADM cell line

STI571, an abl tyrosine kinase inhibitor, is less effective in chronic myelogenous leukemia (CML) patients in the accelerated phase and in blastic crisis. We addressed whether STI571 is effective for the CML blastic crisis cell line K562 and the P-glycoprotein (P-gp) positive, multidrug resistance cell line K562/ADM. The present results demonstrate that P-gp positive K562/ADM cells were more resistant than K562 cells to the anti-proliferative and apoptotic effect of STI571, but the co-addition of a P-gp modulator augmented the sensitivity of K562/ADM cells to STI571. For patients in CML blastic crisis, simultaneous use of a P-gp modulator may increase the efficacy of STI571.