甲基莲心碱对耐阿霉素人乳腺癌细胞凋亡抗性的影响

目的　探讨甲基莲心碱 (neferine ,Nef)对耐阿霉素人乳腺癌细胞 (MCF 7/Adr)凋亡抗性的影响及其机制。方法　应用Tunel法和PI染色流式细胞仪检测细胞凋亡 ,间接免疫荧光流式细胞仪检测P gp的表达 ,高效液相色谱法(HPLC)检测细胞内阿霉素 (ADR)的浓度。结果　①MCF 7/Adr细胞能耐受 5mg·L- 1 ADR诱导的凋亡 ,而 1 ,5 ,1 0μmol·L- 1 Nef可使 5mg·L- 1 ADR诱导的MCF 7/Adr细胞凋亡从 7 95 %分别增加至 2 1 3 % ,2 7 9% ,61 3 % ;② 1 0μmol·L- 1 Nef可使MCF 7/Adr细胞内ADR积累由 0 52 μg·(1 0 6 cells) - 1 增加到 1 50 μg·(1 0 6 cells) - 1 ;③ 1 0 μmol·L- 1Nef作用 2 4h后 ,MCF 7/Adr细胞P gp的表达明显下降。结论　甲基莲心碱能逆转MCF 7/Adr细胞的凋亡抗性 ,其作用机制可能与抑制P gp的功能和表达、增加ADR在MCF 7/Adr细胞内的积累有关     

槲皮素体外逆转白血病细胞耐药性的研究

目的 :探讨槲皮素对白血病细胞多药耐药逆转的影响。方法 :以人白血病细胞系K5 62及耐药细胞系K5 62 A0 2 (耐阿霉素 )为实验对象 ,采用MTT法检测细胞毒性 ,流式细胞仪检测P gp表达水平。结果 :1 0 μmol·L- 1 槲皮素对细胞毒性和P gp的表达无影响 ,2 0、40 μmol·L- 1 槲皮素能明显增强化疗药物对细胞的毒性 ,降低P gp表达的水平。结论 :槲皮素能逆转K5 62 A0 2细胞耐药性     

氟哌啶醇对人红白血病耐多柔比星细胞株多药耐药性的逆转及其机制

目的　从临床常用药物中探寻逆转肿瘤耐药性的活性物质。方法　应用MTT法测定不同浓度Hal处理的瘤细胞对 0～ 2 0 μmol·L- 1多柔比星 (Dox)的敏感性的影响。RT PCR法分析 12 .5 μmol·L- 1氟哌啶醇 (Hal)处理后多药耐药基因 (MDR1) ,多药耐药相关蛋白 (MRP)和谷胱甘肽S转移酶Pi(GSTπ)mRNA表达的变化。通过流式细胞术观察 0 ,6 .2 5 ,12 .5 ,2 5 μmol·L- 1Hal对细胞内药物蓄积和细胞周期进程的影响。结果　Hal对K5 6 2 /Dox的耐药性具有明显的逆转作用。在 12 .5 ,6 .2 5及 3.12 5 μmol·L- 1时的逆转倍数分别为 8.35 ,4 .2 1及 2 .16。用 12 .5μmol·L- 1Hal处理后 ,MDR1及MRP的mRNA表达水平均呈现时间依赖性明显降低 ,分别较原水平下降76 .3%及 6 4.6 %。药后d 2GSTπmRNA表达下降6 6 .1% ,于d 3回升。Hal处理细胞lh后 ,Dox在细胞内蓄积量明显增加 ,并呈浓度依赖性 ;此外 ,Hal可明显增强Dox对K5 6 2 /Dox细胞的G2 /M阻滞作用 ,12 .5 μmol·L- 1浓度可以使 5 μmol·L- 1Dox的G2 /M阻断由单独应用时的 9.9%± 4 .3%增加到2 3.4 %± 3.0 %。结论　Hal具有较强的逆转K5 6 2 /Dox细胞MDR的作用 ,其逆转机制为多种途径 ,包括相关基因mRNA的表达下调 ,增加细胞内药物蓄积 ,增强Dox对K5 6 2 /Dox在G2     

钙调素拮抗剂小檗胺逆转K562／ADR细胞株多药耐药的研究

目的:研究钙调素拮抗剂小檗胺(BBM)抑制白血病细胞增殖并逆转细胞多药耐药的作用。方法:以四唑氮蓝(MTT)法测定小檗胺对K562细胞、耐阿霉素K562细胞(K562/ADR)的增殖抑制作用并求得其IC_(50);测定联合应用阿霉素和BBM后K562/ADR细胞对阿霉素的IC_(50)值及其增敏倍数。采用逆转录聚合酶链反应(RT-PCR)法检测小檗胺作用前后K562/ADR细胞多药耐药基因(MDR)在mRNA水平的表达,应用免疫组织化学方法测定P170表达量。结果:小檗胺能显著抑制K562及K562/ADR细胞增殖,其IC_(50)值分别为5.32 μg·mL~(-1)和 10.97μg·mL~(-1)。联合应用阿霉素和1 μg·mL~(-1)小檗胺使K562/ADR细胞对阿霉素的IC_(50)由5.94 μg·mL~(-1)降低至2.93μg·mL~(-1),其增敏倍数为2.03倍。8 μg·mL~(-1)小檗胺作用K562/ADR细胞24 h后P170的表达量由85.45％降低至63.86％,72 h后MDR1mRNA的表达以β-actin为内参照的半定量比值也由处理前的1.625降至0.877。结论:小檗胺对K562、K562/ADR有显著的增殖抑制作用,小檗胺能部分逆转K562/ADR细胞对阿霉素的耐药,其作用是通过抑制MDR1在mRNA和P170水平的表达而实现的。     

克班宁对耐药细胞K562/HHT逆转作用的研究

目的　对克班宁 (CRE)逆转白血病耐药细胞系K5 6 2 /HHT的耐药性进行研究。方法　细胞毒试验采用MTT法 ,细胞内柔红霉素 (DNR)积累采用荧光分光光度法测定。结果　克班宁 5 μmol·L-1时显著增加高三尖杉酯碱(HHT)对K5 6 2 /HHT的细胞毒 ,细胞毒作用增强 13 0倍 ,同等条件下 8μmol·L-1维拉帕米为 19 4倍。克班宁能显著增加K5 6 2 /HHT细胞内DNR浓度。结论　克班宁通过增加多药耐药细胞内药物积累而调节多药耐药性     

PHⅡ-7逆转肿瘤细胞K562/A02耐药机制的研究

目的阐明PHⅡ-7逆转肿瘤耐药的机制。方法用MTT法测定阿霉素、PHⅡ-7及二者联合用药对人白血病细胞系K562及其多药耐药细胞系K562/A02的IC50值,提取不同浓度PHⅡ-7作用48h后K562和K562/A02细胞RNA,以实时定量PCR的方法分析PHⅡ-7对MDR1基因表达水平的影响,最后通过激光共聚焦显微镜和流式细胞仪观察PHⅡ-7作用前后,K562和K562/A02细胞内阿霉素浓度的改变。结果 PHⅡ-7本身具有抗肿瘤活性,对K562和K562/A02IC50值分别为(1.37±0.37)μmol·L-1;(1.48±0.34)μmol·L-1。此外PHⅡ-7还能协同提高阿霉素的细胞毒作用,K562组CDI值为0.22,K562/A02组CDI值为0.09,其对耐药细胞的协同作用更为明显。阿霉素和PHⅡ-7同时作用于K562/A02,随着PHⅡ-7作用剂量的增加,K562/A02细胞MDR1基因表达水平逐渐下降;细胞内阿霉素浓度伴随PHⅡ-7作用时间的延长而逐渐提高。结论 PHⅡ-7不仅本身是有效的肿瘤细胞化疗药物,还具有下调MDR1耐药基因表达的作用,从而有效逆转K562/A02细胞的耐药现象,增强化疗药物阿霉素的细胞杀伤作用。     

蛇床子素对耐阿霉素人乳腺癌细胞耐药的逆转作用

目的:研究蛇床子素(Ost)对人乳腺癌细胞阿霉素耐药株多药耐药(MDR)的逆转作用及其机制。方法:采用MTT比色法测定药物的细胞毒性,高效液相-紫外检测法检测细胞内ADR浓度。结果:Ost对MCF-7及MCF-7/ADR细胞均有增殖抑制作用,IC50值分别为(58.1±2.3)μmol.L-1和(59±5)μmol.L-1;在5~15μmol.L-1范围内,Ost可以不同程度地增强ADR对MCF-7细胞杀伤作用,与ADR联合用药降低ADR对MCF-7/ADR的IC50值,显著增加MCF-7/ADR细胞内ADR的积累。结论:Ost对人乳腺癌细胞株MCF-7及其阿霉素耐药株MCF-7/ADR细胞均有增殖抑制作用,而且Ost通过明显增加MCF-7/ADR细胞内ADR的浓度,逆转其阿霉素耐药性。     

干扰素与维拉帕米逆转乳腺癌细胞耐药作用的研究

目的:研究α-干扰素与维拉帕米对体外培养的乳腺癌细胞多药耐药(MDR)的逆转作用。方法:以对药物敏感的人乳腺癌细胞系MCF-7和经阿霉素(ADM)诱导具有MDR表型的人乳腺癌耐药细胞系MCF-7/ADR为体外试验模型,分别单用及联用α-干扰素与维拉帕米对细胞系进行处理,MTT法检测各组细胞存活率,计算半数抑制浓度(IC50)、耐药倍数和逆转倍数;流式细胞术定量检测细胞表面P-170的表达。结果:α-干扰素与维拉帕米联用后使乳腺癌细胞耐ADM的IC50降低为0.32μmol·L-1,优于二者单用(2.29、1.23μmol·L-1),逆转倍数升高到51.88(二者单用为7.25、13.49),P-170表达低于二者单用。结论:单独应用α-干扰素、维拉帕米均可达到部分逆转MCF-7/ADR对ADM的耐药作用,但二者联用效果更强。     

环氧化酶-2选择性抑制剂逆转MCF-7/ADR细胞多药耐药的实验研究

目的 研究环氧化酶-2(COX-2)选择性抑制剂Celecoxib对人乳腺癌细胞系MCF-7/ADR的多药耐药(MDR)逆转作用.方法 采用四甲基偶氮唑蓝(MTT)法测定Celecoxib对MCF-7/ADR细胞的无毒剂量,并检测在此剂量下的耐药细胞逆转倍数;荧光分光光度法测定Celecoxib对细胞内阿霉素(ADM)荧光强度的影响.结果 无毒剂量的Celecoxib(1×10-3 μmol/L)可显著降低ADM对MCF-7/ADR的半数抑制浓度(IC50),逆转耐药倍数为1.91倍.Celecoxib能够提高MDR细胞内ADM荧光强度.结论 Celecoxib具有逆转人乳腺癌MCF-7/ADR多药耐药性的作用,可能与增加MDR细胞内化疗药物聚集量有关.     

华蟾素对人乳腺癌细胞阿霉素多药耐药性的逆转作用

目的以耐阿霉素人乳腺癌细胞系MCF-7/ADM为对象,验证华蟾素(cinobufacine,Cino)能否逆转其对阿霉素(ADM)的耐药性。方法采用MTT法检测药物细胞毒性作用及耐药细胞逆转倍数,高效液相色谱法检测细胞内ADM的浓度,流式细胞术测定P-糖蛋白(permeability glycoprotein,P-gp)的表达。结果Cino15mg·L-1能增加MCF-7/ADM细胞对ADM的敏感性,使ADM的半数抑制浓度(IC50)由38.14mg·L-1降至12.93mg·L-1;能提高ADM在MCF-7/ADM细胞内的浓度,降低MCF-7/ADM细胞P-gp的表达。结论研究表明Cino能部分逆转MCF-7/ADM细胞的MDR,其机制与抑制P-gp的功能与表达,增加细胞内ADM的含量有关。     

阿霉素纳米粒对白血病多药耐药细胞株K562/ADR耐药性的逆转作用

目的:研究阿霉素纳米粒对人白血病多药耐药细胞株K562/ADR耐药性的逆转作用.方法:采用MTT法测定药物的体外杀伤作用,应用流式细胞术测定细胞内药物浓度.结果:阿霉素纳米粒和阿霉素对K562细胞细胞毒作用相似,K562/ADR对阿霉素纳米粒较阿霉素敏感2.63倍,细胞内阿霉素浓度显著增加可能是关键因素.结论:阿霉素纳米粒通过增加耐药细胞内阿霉素浓度有效逆转多药耐药.     

屈洛苷芬对K562耐阿霉素细胞株耐药性的逆转作用

目的：研究屈洛昔芬（DRO）对耐阿霉素（ADR）K562细胞株（K562／A02)多药耐药性（MDR）的逆转作用及逆转机制。方法：用DRO分别处理K562／A02和K562敏感株。MTT法观察DRO影响K562／A02对ADR化学敏感性的变化。DRO 10μmol/L处理K562／A02前后,通过RT－PCR和免疫细胞化学染色,分析MDR1、GSTπ基因表达的变化,采用流式细胞技术测定细胞内ADR浓度的变化。结果：DRO显著逆转K562／A02的MDR,在20,10和5μmol/L浓度时,对ADR的化学敏感性分别增加到14、13和4倍,逆转活性与维拉帕米相当。MDR1和GSTπ的mRNA和蛋白表达在DRO 10μmol/L处理后第2天开始下降,第5天明显降低。用20、10和5μmol/L浓度的DRO处理两株细胞,K562／A02细胞内ADR积累分别增加到2．9、2．3和1．5倍。但DRO不能明显增加K562细胞内的ADR的浓度。结论：DRO对K562／A02的MDR有较强的逆转活性,逆转强度与维拉帕米相当,其逆转机制有多种不同的途径。     

Sambutoxin sensitizes K562/ADR to adrimycin by inhibiting expression of P-glycoprotein

OBJECTIVE To investigate the reverse effects of sambutoxin, a representative derivative of 4-hydroxy-2-pyridone with antibacterial, antifungal and antitumor effects, on multidrug resistance(MDR) of K562/ADR cells to adriamycin(ADR) and to elucidate its potential molecular mechanism. METHODS We first investigated the dose-dependent cytotoxic effects of sambutoxin as single treatment on K562 and K562/ADR cells by MTT and CCK-8 assay in order to select the suitable dosage of sambutoxin in the combination treatment. The cytotoxicity of ADR combined with sambutoxin on K562 and K562/ADR cells were also determined by MTT and CCK-8 assays. Then, effects of sambutoxin on the intracellular accumulation of ADR in K562/ADR cells were determined using flow cytometry. The effect of sambutoxin on the efflux function and expression of P-gp in K562/ADR cells was evaluated by Rhodamine123(Rh123) accumulation assay and Western blotting assay respectively. 3 D interactions of human P-gp with sambutoxin, verapamil and adriamycin predicted by docking studies conducted using Sybyl2.1 sofware. Next, the effect of combination treatment of sambutoxin and ADR on the apoptosis of K562/ADR cells was determined by Hoechst 33342 nuclear staining. The expression of the apoptosis related proteins were detected by Western blotting assay. Effect of sambutoxin and ADR on reactive oxygen species(ROS) level in K562/ADR cells was evaluated detected by the DCFH-DA method using fluorescence microscopy and flow cytometry. Effect of sambutoxin and ADR on EGFR/MAPK and PI3 K/AKT/m TOR signaling pathways in K562/ADR cells was evaluated by Western blotting assay. RESULTS Sambutoxin treatment potently enhanced the susceptibility of K562/ADR cells to ADR in a dose manner and the reversal effect was much more prominent in K562/ADR cells. Sambutoxin increased the intracellular accumulation of ADR and Rh123 in K562/ADR cells. Sambutoxin inhibited protein expression of P-gp through Akt/NF-κB pathway in K562/ADR cells. Molecular docking display sambutoxin with P-gp(PDB code:6 QEX) formed two hydrogen bonds with GLN-725 and ASN-721, total Score was 8.29. Co-administration ADR with sambutoxin remarkably increased ADR-induced apoptosis through mitochondrial pathway, including down-regulation of anti-apoptotic protein Bcl-2, up-regulation of proapoptotic protein Bax, up-regulation of cleaved caspase3, and cleaved PARP, augmented ROS in K562/ADR cells. Moreover, ADR combined with sambutoxin could down-regulate the EGFR/MAPK and PI3 K/AKT/m TOR survival pathway in K562/ADR cells. CONCLUSION Sambutoxin reverses MDR of K562/ADR cells to ADR by downregulating P-gp expression and increasing ROS level, as well as, inducing apoptosis. These fundamental findings provide evidence for further clinical research in application of sambutoxin as an assistant agent for chemotherapy of cancer.     

抗多药耐药基因肽核酸与反义寡脱氧核苷酸增强K562／ADM细胞的敏感性和促进凋亡

AIM: To investigate the reversal effect and apoptosis enhancement of peptide nucleic acid (PNA) and antisenseoligodeoxyribonucleotide (ASODN) targeted to multidrug resistance gene (mdrl) on human multidrug resistantleukemia K562/ADM cells. METHODS: A 15-mer PNA and the same sequence of ASODN, complementary to the5' end of the AUG initiator codon-containing region of mdrl messenger RNA (MDR1-PNA, MDR1-ASODN), weredesigned and synthesized. Proliferation and sensitivity to adriamycin of K562/ADM cells treated with MDRI-PNAand MDR1-ASODN were analyzed with a MTT colorimetric assay. Apoptotic morphologies, P-glycoprotein (P-gp)expression, intracellular adriamycin accumulation, and cell cycle were measured. RESULTS: MDRI-PNA 1 to 10μmol/L and MDR1-ASODN 2 to 20 μmol/L alone had no inhibitory effects on the proliferation of K562/ADM cells,but significantly inhibited the growth of K562/ADM cells cultured in adriamycin-containing medium. After treatment with MDRI-PNA and MDRI-ASODN, intracellular adriamycin accumulation in K562/ADM cells increasedgreatly and P-gp synthesis was strikingly reduced. The resistance to adriamycin of the drug-resistant cells waspartly reversed and the cells were induced to apoptosis by adriamycin. The reversal efficacy of MDR1-PNA was3.1-fold higher than that of the same sequence of MDR-ASODN, but neither MDRI-PNA nor MDRI-ASODNcould completely block the mdrllP-gp expression. CONCLUSION: Sequence-special PNA targeted to mdr1 genemore effectively than the same sequence of MDR1-ASODN inhibited the expression of P-glycoprotein to overcomethe drug-resistance.     

复方藤梨根制剂体外对MDR细胞株K562/ADR和K562/VCR细胞积聚和外排阿霉素(ADR)的影响研究

目的 :探讨复方藤梨根制剂 (FFTLG)对肿瘤化疗增敏的作用机理。方法 :以MTT法观察FFTLG对MDR细胞的逆转作用 ,以FCM技术测定FFTLG作用MDR细胞后对阿霉素的积聚和外排影响。结果 :10mg/ml和 2 0mg/ml的FFTLG对K5 6 2 /ADR的逆转倍数是 7.5 3和 10 .31倍 (P <0 .0 5 ) ;2 0mg/ml的FFTLG对K5 6 2 /VCR的逆转倍数是 6 .18倍 ;10mg/ml和2 0mg/ml的FFTLG可增加K5 6 2 /ADR和K5 6 2 /VCR细胞内ADR的积聚分别是 77.6 % ,80 .1%和 5 0 .9% ,4 5 .2 % ,且可减少ADR的外排。结论 :FFTLG通过增加MDR细胞内的ADR积聚及减少外排机制而实现对化疗的增敏作用     

Ligustrazine derivate DLJ14 reduces multidrug resistance of K562/A02 cells by modulating GSTπ activity

Multidrug resistance (MDR) of tumor cells is a major obstacle in chemotherapeutic cancer treatment. Over-expression of glutathione S-transferase π (GSTπ) is one of the mechanisms contributing to MDR. In this study, we investigated the reversal of MDR by DLJ14, a ligustrazine derivate, in adriamycin (Adr) resistant human myelogenous leukemia (K562/A02) cells by modulating the expression of GSTπ and the activity of GST-related enzymes. In the MTT test, DLJ14 showed a weak inhibition on proliferation of both K562/A02 and K562 cells, while verapamil at the same concentration showed a much stronger inhibition. The sensitivity of K562/A02 cells to cytotoxic killing by Adr was enhanced by incubation with DLJ14 as a result of the increased intracellular accumulation of Adr. The accumulation of Adr induced by DLJ14 may due to down regulation of GST-related enzyme activity. Western blot analysis and RT-PCR showed that DLJ14 was able to inhibit the protein expression and mRNA expression of GSTπ in K562/A02 cells. Moreover, DLJ14 increased the expression of cellular c-Jun NH₂-terminal kinase (JNK) in K562/A02 cells exposure to Adr. This is consistent with the inhibition of GSTπ. These results demonstrate that DLJ14 may be an attractive new agent for the chemosensitization of cancer cells.     

洛美利嗪逆转K562/ADM细胞多药耐药性

目的研究洛美利嗪(lomerizine,Lom)逆转K562/ADM细胞多药耐药性的作用及机制。方法MTT法检测细胞毒作用,流式细胞仪研究Lom对ADM和长春新碱(vincristine,VCR)的K562/ADM细胞凋亡诱导作用的影响及对罗丹明123(rhodamine 123,Rh123)外排和P-糖蛋白(P-glycoprotein,P-gp)表达的作用。结果Lom明显提高ADM对K562/ADM多药耐药细胞的细胞毒作用及ADM和VCR的凋亡诱导作用,3,10和30 μmol·L^-1 Lom使K562/ADM对ADM的IC₅₀值由79.03 μmol·L^-1分别降至28.14,8.16和3.16 μmol·L^-1。Lom增加胞内ADM的蓄积浓度并抑制Rh123外排;但作用72 h后对K562/ADM细胞P-gp表达无影响。结论Lom通过抑制P-gp的活性逆转K562/ADM细胞的多药耐药性。     

五味子甲素对K562/ADR、HL60/ADR、MCF-7/ADR多药耐药逆转机制的研究

目的探讨五味子甲素(schizandrin A or deoxyschizan-drin,schA)对白血病细胞K562/ADR、HL60/ADR、乳腺癌细胞MCF-7/ADR多药耐药的逆转作用,并初步探讨其逆转机制。方法 MTT法检测schA对耐药细胞的逆转作用;流式细胞仪检测schA对细胞内柔红霉素、罗丹明-123含量和细胞表面P-gp表达水平的变化;用Real-time PCR方法检测schA对细胞内mdr1 mRNA和mrp1 mRNA表达;生化检测法检测schA对细胞内GSH含量的变化。结果耐药逆转实验显示:不同浓度的schA对作用机制不同的化疗药物耐药产生不同的逆转效果;蓄积实验表明schA可增加柔红霉素、罗丹明123在耐药细胞内的蓄积,并且有良好的剂量依赖关系;schA处理K562/ADR、HL60/ADR细胞24 h后,能降低P-gp蛋白和mdr1、mrp1基因的表达;schA处理K562/ADR、HL60/ADR细胞4 h后,可降低细胞内谷胱甘肽含量。结论 schA对耐药机制不同的细胞株K562/ADR、HL60/ADR均有耐药逆转作用,推测可能是与抑制细胞表面的P-gp蛋白功能和表达,降低mdr1、mrp1耐药基因的表达和降低细胞内谷胱甘肽含量有关,schA通过影响上述机制,进而增加细胞内的药物浓度,达到有效杀灭肿瘤细胞的作用。     

盐酸千金藤碱逆转K562/ADR细胞多药耐药性及其机制

研究盐酸千金藤碱(cepharanthine hydrochloride,CH)逆转K562/ADR细胞多药耐药性及其机制。采用MTT法检测多柔比星(adriamycin,ADR)单用及分别与CH、维拉帕米(verapamil,VER)合用的细胞毒作用;采用流式细胞仪,测定CH对细胞内ADR蓄积、罗丹明123(Rho123)蓄积和泵出及P糖蛋白(P-gp)表达的影响。结果表明,CH(4μmol.L1)使K562/ADR细胞对ADR的敏感性增加7.43倍,逆转活性是VER的3.19倍,但对K562敏感株基本无影响。同时CH浓度依赖性地增加K562/ADR细胞内ADR和Rho123的蓄积,减少Rho123的泵出,抑制P糖蛋白的表达,但对K562细胞均无明显影响。CH在体外逆转肿瘤细胞多药耐药性的作用可能与其抑制P糖蛋白的功能和表达有关。     

FAT对K562/A02细胞内GSH含量的影响

目的：探讨FAT对K562/A02细胞内谷胱甘肽（GSH）含量的影响,及其对白血病细胞代谢解毒系统介导的多药耐药（MDR）的逆转效果。方法：采用生化DTNB法测定细胞内谷胱甘肽水平。结果：K562/A02细胞内GSH含量（231.54μmol/106细胞）高于K562细胞内GSH含量（58.03μmol/106细胞）,为K562细胞的3.99倍;VRP（10μmol/L）、FAT（0.01、0.02、0.04、0.08mg/ml）作用48h后,K562/A02细胞内GSH含量从231.54μmol/106细胞分别减少到96.95μmol/106细胞、212.89μmol/106细胞、161.00μmol/106细胞、122.35μmol/106细胞。结论：细胞内GSH含量增加是K562/A02细胞产生MDR的机制之一;FAT降低K562/A02细胞内GSH的含量是FAT逆转MDR的机制之一。