The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells

PURPOSE: This study aimed to evaluate the multidrug resistance (MDR) reversal activity of quercetin (Que) in combination with hyperthermia (HT) in human myelogenous leukemia cells K562/A. METHODS: The cytotoxicity of Que alone and the effect of Que and HT to doxorubicin (Dox) cytotoxicity were determined using MTT assay in K562 and K562/A cells. K562/A cells was heated with or without Que pretreatment, and the protein and mRNA levels of heat shock protein 70 (HSP70) and P-glycoprotein (P-gp) were determined by flow cytometry (FCM) and RT-PCR, respectively. Intracellular accumulation of Dox, cell cycle and apoptosis were monitored with FCM. RESULTS: Que alone inhibited cell growth in a dose-dependent manner in K562 and K562/A cells. Either Que or HT alone had a weak reversal effect on Dox resistance, however, combination HT and Que showed a much more significant reversal effect on Dox resistance (reverse fold 9.49). The elevated protein expression and mRNA level of HSP70 and P-gp in response to HT were inhibited by Que. Pretreatment with Que caused the cells to accumulate Dox 8.3-fold higher than in control cells. In addition, Que induced apoptosis and G2/M arrest in a dose-dependent manner, and the combination of Que and HT was found to have a synergistic effect on apoptosis. CONCLUSIONS: Que pretreatment could significantly enhance the MDR reversal activity of HT in resistant cell line, by sensitizing the cell to reversing MDR activity of HT.     

The synergistic reversal effect of multidrug resistance by quercetin and hyperthermia in doxorubicin-resistant human myelogenous leukemia cells

Purpose: This study aimed to evaluate the multidrug resistance (MDR) reversal activity of quercetin (Que) in combination with hyperthermia (HT) in human myelogenous leukemia cells K562/A.

Methods: The cytotoxicity of Que alone and the effect of Que and HT to doxorubicin (Dox) cytotoxicity were determined using MTT assay in K562 and K562/A cells. K562/A cells was heated with or without Que pretreatment, and the protein and mRNA levels of heat shock protein 70 (HSP70) and P-glycoprotein (P-gp) were determined by flow cytometry (FCM) and RT-PCR, respectively. Intracellular accumulation of Dox, cell cycle and apoptosis were monitored with FCM.

Results: Que alone inhibited cell growth in a dose-dependent manner in K562 and K562/A cells. Either Que or HT alone had a weak reversal effect on Dox resistance, however, combination HT and Que showed a much more significant reversal effect on Dox resistance (reverse fold 9.49). The elevated protein expression and mRNA level of HSP70 and P-gp in response to HT were inhibited by Que. Pretreatment with Que caused the cells to accumulate Dox 8.3-fold higher than in control cells. In addition, Que induced apoptosis and G2/M arrest in a dose-dependent manner, and the combination of Que and HT was found to have a synergistic efeect on apoptosis.

Conclusions: Que pretreatment could significantly inhance the MDR reversal activity of HT in resistant cell line, by sensitizing the cell to reversing MDR activity of HT.     

Reversal of the resistance to STI571 in human chronic myelogenous leukemia K562 cells

STI571, an Abl-specific tyrosine kinase inhibitor, selectively kills Bcr-Abl-containing cells in vitro and in vivo . However, some chronic myelogenous leukemia (CML) cell lines are resistant to STI571. We evaluated whether STI571 interacts with P-glycopro-tein (P-gp) and multidrug resistance protein 1 (MRP1), and examined the effect of agents that reverse multidrug resistance (MDR) on the resistance to SI571 in MDR cells. STI571 inhibited the [¹²⁵l]azidoagosterol A-photolabeling of P-gp, but not that of MRP1. K562/MDR cells that overexpress P-gp were 3.67 times more resistant to STI571 than the parental Philadelphia-chromosome-positive (Ph+) CML K562 cells, and this resistance was most effectively reversed by cepharanthine among the tested reversing agents. The concentration of STI571 required to completely inhibit tyrosine phosphorylation in K562/MDR cells was about 3 times higher than that in K562 cells, and cepharanthine abolished the difference. In KB-G2 cells that overexpress P-gp, but not Bcr-Abl, 2.5 μM STI571 partly reversed the resistance to vincristine (VCR), paclitaxel, etoposide (VP-16) and actinomycin D (ACD) but not to Adriamycin (ADM) or colchicine. STI571 increased the accumulation of VCR, but not that of ADM in KB-G2 cells. STI571 did not reverse resistance to any agent in KB/MRP cells that overexpress MRP1. These findings suggest that STI571 is a substrate for P-gp, but is less efficiently transported by P-gp than VCR, and STI571 is not a substrate for MRP1. Among the tested reversing agents that interact with P-gp, cepharanthine was the most effective agent for the reversal of the resistance to STI571 in K562/ MDR cells. Furthermore, STI571 itself was a potent reversing agent for MDR in P-gp-expressing KB-G2 cells.     

Experimental Study on the Mechanism of Reversal of Leukemia Multidrug Resistance by Proteasome Inhibitor Bortezomib

OBJECTIVE In this study, we applied multidrug resistant leukemia cell line expressing mdr1-mRNA to observe changes in mdr1-mRNA, the P-gp, cell cycle and apoptosis before and after bortezomib was used, in order to explore the mechanism of reversal of leukemia multidrug resistance by the proteasome inhibitor bortezomib.METHODS Flow cytometry (FCM) was used to detect the intracellular drug concentration, expression of P-gp, cell apoptosis and cell cycle status of K562/DNR cells before and a er treatment with different concentrations of bortezomib. Fluorescence quantitative PCR was applied to detect the mdr1-mRNA expression in K562/DNR and K562/S cells.RESULTS Bortezomib could increase the intracellular DNR content in K562/DNR cells, but showed no e. ect in K562/S cells.5-100 nmol/L bortezomib could significantly reduce the P-gp/mdr1-mRNA expression in K562/DNR cells in vitro, and showed a dose-dependent effect. There was a statistically significant di. erence (P < 0.05) between di. erent concentration groups and the control group. P-gp/mdr1-mRNA expression was negatively correlated with cell apoptosis (r = -0.912 and P < 0.01). After treatment with different concentrations of bortezomib for 24 h,K562/DNR cells in G2 + M phases were significantly increased,while cells in G0 + G1 phases and S phase were significantly decreased, accompanied by an increased apoptotic rate.CONCLUSION Bortezomib can induce G0 + G1 phase to G2 + M phase, and thereby enhance the chemosensitivity of leukemia, and may also reverse the multidrug resistance in leukemia mediated by P-gp overexpression encoded by mdr1 gene. This confi rms that bortezomib can reverse leukemia multidrug resistance at the levels of nucleic acid and protein molecules.     

RNAi对白血病细胞mdr-1基因和多药耐药表型的影响

目的:探讨RNA干扰技术(RNAi)对慢性粒细胞白血病急变细胞系K562/AO2细胞mdr1基因的抑制和耐药表型的逆转作用。方法:选择合成封闭mdr-1基因的小干扰序列(si-MDR1),以1个碱基突变的si-MDR1-mut为对照序列,在脂质体介导下转染至K562/AO2细胞系。RT-PCR和Western blot检测mdr1 mRNA及P-gp蛋白水平,流式细胞术分析细胞内柔红霉素(daunorubicin,DNR)积累量,并以四甲基唑蓝快速比色法(MTT)反映K562/AO2对阿霉素、长春新碱、足叶乙甙药物敏感性的变化。结果:实验证实该序列能高效封闭K562/AO2细胞内mdr-1基因表达,增加细胞内化疗药物DNR积累量,增强K562/AO2细胞对阿霉素、长春新碱、足叶乙甙的敏感性。结论:RNAi可以通过抑制mdr1基因表达,逆转K562/AO2细胞耐药表型。     

环孢素A对白血病耐药细胞化疗药物敏感性的研究

目的 研究环孢素A对K562/DOX细胞多药耐药的逆转作用.方法 用流式细胞仪和MTT法观察了CsA对K562/DOX细胞P-糖蛋白的抑制作用及对阿霉素(doxorubicin,DOX)、长春新碱(vincristine,VCR)耐药的逆转作用.结果 CsA能剂量相关性地增加K562/DOX细胞内罗丹明123(rhodamine123,Rh123)的累积,明显抑制P-gp介导的Rh123外排,显著增强DOX、VCR的细胞毒作用,增加VCR诱导的细胞凋亡和G2/M期细胞百分率.结论 CsA能显著抑制P-gp的外排功能,逆转K562/DOX细胞的多药耐药性.     

Cepharanthine potently enhances the sensitivity of anticancer agents in K562 cells

A major impediment to cancer treatment is the development of resistance by the tumor. P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) are involved in multidrug resistance. In addition to the extrusion of chemotherapeutic agents through these transporters, it has been reported that there are differences in the intracellular distribution of chemotherapeutic agents between drug resistant cells and sensitive cells. Cepharanthine is a plant alkaloid that effectively reverses resistance to anticancer agents. It has been previously shown that cepharanthine is an effective agent for the reversal of resistance in P-gp-overexpressing cells. Cepharanthine has also been reported to have numerous pharmacological effects besides the inhibition of P-gp. It has also been found that cepharanthine enhanced sensitivity to doxorubicin (ADM) and vincristine (VCR), and enhanced apoptosis induced by ADM and VCR of P-gp negative K562 cells. Cepharanthine changed the distribution of ADM from cytoplasmic vesicles to nucleoplasm in K562 cells by inhibiting the acidification of cytoplasmic organelles. Cepharanthine in combination with ADM should be useful for treating patients with tumors.     

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.     

The inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in chronic myelogenous leukemic K562 cells

In this study, the downstream signaling of Bcr-Abl tyrosine kinase responsible for apoptosis resistance was investigated. DNA fragmentation, a hallmark of apoptosis, was observed after 2 days of herbimycin A treatment with a peak on 3 day. During the apoptosis induced by the treatment of herbimycin A, stress-activated protein kinase (SAPK) and p38 kinase were activated time- and dose-dependently, while extracellular signal-regulated kinase (ERK) was inhibited. However, apoptosis was induced by the treatment of PD98059, a specific inhibitor of MEK (MAPK or ERK kinase), not by the treatment of sorbitol, a strong activator of SAPK and p38 kinase. Although K562 cells were very resistant to sorbitol-induced apoptosis, DNA fragmentation was induced rapidly in Jurkat, HL-60 and U937 cells after exposure to sorbitol, despite that these apoptosis-sensitive cells have similar or lower activities of JNK/SAPK and p38 kinase compared with K562 cells after treatment of sorbitol. K562 cells had a much higher basal activity of ERK/MAPK than other apoptosis-sensitive cell lines, which were very susceptible to apoptosis induced by low dose of PD98059 compared with K562 cells. In HL-60 cells, sorbitol-induced apoptosis was prevented by the treatment of phorbol myristate 13-acetate (PMA), which activates the ERK/MAPK pathway, and this was blocked by PD98059. From these results, it could be suggested that the inhibition of ERK/MAPK not the activation of JNK/SAPK is primarily required to induce apoptosis in K562 cells.     

Reversal of P-glycoprotein mediated multidrug resistance by a newly synthesized 1,4-benzothiazipine derivative,JTV-519

A newly synthesized 1,4-benzothiazipine derivate, 4-[3-(4-benzylpiperidin-1-yl) propionyl]-7-methoxy-2,3,4,5-tetrahydro-1, 4-benzothiazepine monohydrochloride (JTV-519) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) mediated multidrug resistance (MDR) in K562/MDR and KB/MRP cells, respectively. JTV-519 at 3 microM reversed the resistance of K562/MDR cells to vincristine (VCR), taxol, etoposide (VP16), adriamycin (ADM) and actinomycin D and at 0.5 or 1 microM reversed their resistance to STI571. JTV-519 at 10 microM enhanced the accumulation of ADM in K562/MDR cells to the level in parental K562 cells and inhibited the efflux of ADM from K562/MDR cells. Photoaffinity labeling of P-gp with 3H-azidopine was almost completely inhibited by 500 microM JTV-519. JTV-519 at 3 microM also partially reversed the resistance of KB/MRP cells to VCR and at 500 microM partially inhibited the photoaffinity labeling of MRP1 with (125)I-II-azidophenyl agosterol A (125I-azidoAG-A). These results suggest that JTV-519 reversed the resistance to the anti-cancer agents in P-gp and MRP1 overexpressing multidrug-resistant cells by directly binding to P-gp and MRP1, and competitively inhibiting transport of the anti-cancer agents.     

干扰素和环孢霉素A 协同逆转K562/ ADM细胞对阿霉素的耐药性

  目的 观察干扰素(α-Interleron，α-IFN)和环孢霉素A(Cyclosporine A,CsA)对白血病K562/ADM细胞耐药性的协同逆转效应。方法 以多药耐药基因／P-糖蛋白(Muhidrug resistance gene／P-glycoprotein，mdrl／P-gp)超表达的K562／ADM细胞为靶细胞，MTT比色法检测药物的细胞毒效应；流式细胞仪检测细胞P-糖蛋白(P-glycoprotein，P-gp)表达水平；激光共聚焦显微镜观察细胞内阿霉素含量变化。结果 K562／ADM细胞对阿霉素呈高度耐药性，并与柔红霉素和鬼臼乙叉甙交叉耐药，但与CsA无交叉耐药。CsA和α-IFN单独或联合应用均对K562／ADM细胞的耐药性有较强的抑制效应。流式细胞仪和激光共聚焦显微镜分析发现α-IFN和CsA单独或联合均不能下调细胞mdrl/P-gp的表达，反而应激性地刺激耐药细胞P-gp的合成增加，但可抑制P-gp的功能、增加K562／ADM细胞内阿霉素的积聚。结论 α-IFN和CsA联合可协同逆转耐药白血病细胞的耐药性，其作用机制为抑制P-gp的功能而非下调mdrl／P-gp的表达水平。     

汉防己甲素联合屈洛昔芬逆转K562/A02细胞耐药与诱导凋亡

目的探讨汉防己甲素(Tet)联合屈洛昔芬(Drol)对耐药细胞系K562/A02的逆转作用及其与诱导凋亡的关系.方法采用甲基四唑蓝法(MTT)测定柔红霉素(DNR)的细胞毒性;采用DNA凝胶电泳法观察Tet、Drol单独及联合应用对K562/A02细胞凋亡诱导作用的影响.结果 0.62 μg/ml Tet、1.94 μg/ml Drol均能增加DNR对K562/A02的细胞毒作用,其半数抑制量IC50分别为7.28±2.06 μg/ml和7.58±3.44 μg/ml,逆转倍数分别为2.94倍和2.82倍.两药联合作用明显增强,其IC50为1.66±0.41 μg/ml,逆转倍数达12.9倍.0.62 μg/ml Tet、1.94 μg/ml Drol单独及联合应用均不会诱导K562/A02细胞凋亡.结论单独应用Tet、Drol可部分逆转K562/A02细胞的耐药性,两药联用具有明显协同效应.Tet、Drol逆转耐药的机理与诱导K562/A02细胞凋亡无关.     

Expression of p-glycoprotein in multidrug-resistant human leukemia k562 cells during erythroid-differentiation

Expression of P-glycoprotein (P-gp), the multidrug resistance gene product, has previously been shown to be downregulated during differentiation of normal haematopoietic cells. In order to determine whether such a regulation also occurs in leukemic cells, we have investigated the relevance of differentiation levels to P-gp expression in multidrug-resistant leukemia K562R/7 cells and in parental drug-sensitive K562 cells. These leukemic cells were exposed to hemin and sodium butyrate, two known inducers of erythroid differentiation. Analysis of hemoglobin-synthesizing cells indicated that hemin induced both K562R/7 and K562 cells to differentiate into erythroid cells while sodium butyrate led to hemoglobin synthesis in only K562 cells. Northern blotting and immunolabelling experiments revealed elevated levels of MDR1 mRNAs and P-gp in both untreated and hemin-treated K562R/7 cells while P-gp expression was not detected in both uninduced and hemin-induced K562 cells. Flow cytometric analysis of cellular doxorubicin retention demonstrated that K562R/7 cells poorly accumulated the anticancer drug regarless their level of differentiation. These results therefore suggest that erythroid differentiation of leukemic drug-resistant K562R/7 cells in response to hemin treatment did not result in major alteration of P-gp expression and activity.     

Antitumor effects of cytosine deaminase and thymidine kinase fusion suicide gene under the control of mdr1 promoter in mdr1 positive leukemia cells

The multidrug resistance (mdr) mediated by P-glycoprotein (P-gp), the mdr1 gene product, is one of the major obstacles in leukemia treatment. The present study was designed to explore a suicide gene therapy approach targeting mdr1 for reversal of P-gp-mediated mdr in the mdr positive K562/A02 cells. To study targeted killing effects of cytosine deaminase (CD)-thymidine kinase (TK) fusion suicide gene on multi-drug resistant leukemia, the CD-TK fusion suicide gene expression vector driven by mdr1 promoter was constructed and transferred into K562 and K562/A02 cells using lipofectintrade mark 2000. RT-PCR was used to demonstrate that there were CD and TK genes expression in K562/A02 cells, but not in K562 cells. MTT analysis showed that, compared with that in K562/CDTK, the survival rate of K562/A02-CDTK cells decreased and at the same time the apoptotic rate increased after treatment with GCV and 5-FC (P < 0.05). In vivo studies showed that the tumor volume in the prodrug treated K562/A02-CDTK groups was significantly less than that in the NS-control and K562-CDTK groups (P < 0.05). These findings show that the CD and TK fusion suicide gene expression driven by mdr1 promoter is effective in killing multidrug resistant K562/A02 cells.     

Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1.

The multidrug resistance (MDR) phenotype, induced by the overexpression of several ABC transporters or by antiapoptotic mechanisms, has been identified as the major cause of drug resistance in the treatment of patients with acute myeloid leukemia (AML). In this study, we have shown that valproic acid (VPA) (a histone deacetylase inhibitor) can inhibit the proliferation of both P-glycoprotein (P-gp)- and MDR-associated protein 1 (MRP1)-positive and -negative cells. VPA also induced apoptosis of P-gp-positive cells. VPA induced apoptosis in K562 cells led to decrease in Flip (FLICE/caspase-8 inhibitory protein) expression with Flip cleavage, which could not be observed in HL60 cells. In HL60/MRP cell line, which proved to be resistant to apoptosis by VPA, we observed an abnormal expression of apoptotic regulatory proteins, overexpression of Bcl-2 and absence of Bax. Also, the Bcl-2 antagonist HA14-1 rapidly restored apoptosis in this cell line. Cotreatment with cytosine arabinoside induced very strong apoptosis in both K562/DOX and HL60/DNR cell lines. VPA also induced apoptosis in AML patient cells expressing P-gp and/or MRP1. Our findings show VPA as an interesting drug that should be tested in clinical trials for overcoming the MDR phenotype in AML patients.     

NF-κB信号通路的激活对白血病细胞K562／A02多药耐药的影响

 目的　研究K562细胞株及其耐药细胞株K562／A02 NF-κB活性的差异性表达,探讨白血病多药耐药（MDR）发病机制。方法　用MTT法检测K562／A02的耐药倍数,观察细胞生长的形态学变化,PI单染法检测K562／S、K562／A02细胞周期分布,并用RT-PCR 方法检测mRNA的表达、流式细胞仪检测P糖蛋白（P-gp）表达及其功能,Western blotting方法检测细胞核NF-κB p65表达,比较K562与K562／A02白血病耐药细胞株之间的差异性。结果　与K562细胞不同,耐药细胞株K562／A02细胞生长特性发生改变,呈半贴壁生长,与K562／S细胞相比,K562／A02细胞的 G0／G1期、S期比例增高,G2／M期细胞比例减低,差异有统计学意义（P＜0.05）,凋亡细胞比例差异无统计学意义（P＞0.05）,且检测到mdr1 mRNA及细胞膜P-gp表达增高以及细胞核内NF-κB p65表达明显增加。结论　NF-κB信号通路的激活即NF-κB p65细胞核内转位可能参与了白血病MDR的形成。     

5-溴汉防己甲素与汉防己甲素对K562/A02细胞多药耐药性逆转作用的比较

背景与目的:5-溴汉防己甲素(5-bromotetrandrine,BrTet)是汉防己甲素(tetrandrine,Tet)的溴化产物,具有逆转P-糖蛋白(P-glyeoprotein,P-gp)介导的肿瘤多药耐药(muhidrug resistance,MDR)的作用。本研究旨在比较BrTet与Tet对人白血病细胞K562/A02多药耐药的逆转作用。方法:采用四甲基偶氮唑蓝法(MTT)法检测不同浓度BrTet对K562细胞和K562/A02细胞的增殖抑制效应;检测阿霉素(adfiamycin,ADM)对K562细胞和K562/A02细胞增殖的抑制作用,以及加用BrTet、Tet时上述抑制作用的变化,并计算半数抑制浓度(IC50)及逆转倍数。Westernblot法检测各组细胞P-gp的表达,流式细胞仪检测各组细胞内ADM的蓄积。结果:K562/A02细胞对ADM的耐药倍数为49.51倍。2.0μmol/L及更低浓度的BrTet和1.5μmol/L及更低浓度的Tet对K562细胞和K562/A02细胞抑制率均小于10%,无明显细胞毒性作用。加入1.0μmol/L的Tet后,K562/A02细胞对ADM的耐药倍数为12.17倍。加入0.25、0.5和1.0μmol/L的BrTet后,K562/A02细胞对ADM的耐药倍数分别为17.88、9.97和4.24倍。1.0"mol/L的BrTet和Tet分别使K562/A02细胞内ADM浓度提高了69.0%和51.6%,使P-gp表达分别下调了51.1%和43.73%,其差异具有统计学意义(P<0.05)。结论:BrTet及Tet均可逆转K562/A02细胞耐药,且前者较后者逆转作用更强,逆转机制与抑制P-gp的表达、增加细胞内抗肿瘤药物浓度有关。     

Asparaginase induces apoptosis and cytoprotective autophagy in chronic myeloid leukemia cells

The antitumor enzyme asparaginase, which targets essential amino acid L-asparagine and catalyzes it to L-aspartic acid and ammonia, has been used for years in the treatment of acute lymphoblastic leukemia (ALL), subtypes of myeloid leukemia and T-cell lymphomas, whereas the anti-chronic myeloid leukemia (CML) effect of asparaginase and its underlying mechanism has not been completely elucidated. We have shown here that asparaginase induced significant growth inhibition and apoptosis in K562 and KU812 cells. Apart from induction of apoptosis, we reported for the first time that asparaginase induced autophagic response in K562 and KU812 cells as evidenced by the formation of autophagosome, microtubule-associated protein light chain 3 (LC3)-positive autophagy-like vacuoles, and the upregulation of LC3-II. Further study suggested that the Akt/mTOR (mammalian target of rapamycin) and Erk (extracellular signal-regulated kinase) signaling pathway were involved in asparaginase-induced autophagy in K562 cells. Moreover, blocking autophagy using pharmacological inhibitors {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, chloroquine (CQ) and quinacrine (QN) enhanced asparaginase-induced cell death and apoptosis, indicating the cytoprotective role of autophagy in asparaginase-treated K562 and KU812 cells. Together, these findings provide a rationale that combination of asparaginase anticancer activity and autophagic inhibition might be a promising new therapeutic strategy for CML.     

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.