双苄基异喹啉类生物碱粉防己碱与小檗胺逆转多药抗药性的比较研究

比较了2种结构相近的双苄基异喹啉(BBI)生物碱粉防己碱(TTD)、小檗胺(BBM)与维拉帕米(VRP)逆转多药抗药性的作用。结果,TTD,BBM和VRP在多药抗药的MCF-7/Adr和KBv₂₀₀细胞对ADR和VCR均有明显增敏作用,且作用呈剂量依赖性。其中10μmol·L^-1TTD能完全逆转MCF-7/Adr细胞对ADR的抗药性。TTD,BBM和VRP均有增加MCF-7/Adr细胞内阿霉素积累的作用。TTD和BBM在结构上仅有微小差别,但TTD的逆转MDR作用优于VRP10倍,而BBM的作用与VRP相仿。TTD在裸鼠体内MCF-7/Adr实体瘤模型上也证实有明显逆转ADR抗药性的作用。     

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。     

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.     

叶酸受体及二氢叶酸还原酶与人乳腺癌细胞MCF-7/ADR多药耐药的关系

目的以人乳腺癌多药耐药细胞系MCF-7/ADR及其敏感亲本系MCF-7为对象,探讨叶酸受体(FOLRα)及其下游基因二氢叶酸还原酶(DHFR)的表达与乳腺癌细胞多药耐药的关系。方法 MTT法测定阿霉素的细胞毒性作用及DHFR抑制剂对MCF-7/ADR细胞多药耐药的逆转作用;RT-PCR检测细胞FOLRα和DHFR mRNA的表达水平;免疫细胞化学检测FOLRα、P-gp的表达水平。结果 MCF-7细胞增殖速度快于MCF-7/ADR细胞,MCF-7细胞FOLRα mRNA转录水平较MCF-7/ADR细胞高,而MCF-7/ADR细胞DHFR mRNA较MCF-7细胞转录水平高;免疫细胞化学显示MCF-7细胞FOLRα的表达高于MCF-7/ADR细胞,而MCF-7/ADR细胞P-gp的表达较MCF-7细胞高;MCF-7/ADR对甲氨蝶啶无耐药性,甲氨蝶啶对MCF-7/ADR细胞多药耐药有逆转作用。结论 MCF-7/ADR细胞FOLRα的表达水平下调可能与细胞增殖水平有关,其下游基因DHFR表达水平与MCF-7/ADR细胞的MDR可能存在相关性。     

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。     

钙调素拮抗剂O-(4-乙氧基)-丁基-小檗胺增强阿霉素杀伤MCF-7/ADR细胞的机制研究

目的研究钙调素拮抗剂0-4-乙氧基-丁基-小檗胺(EBB)增强阿霉素诱导乳腺癌多药耐药细胞系MCF-7/ADR细胞的杀伤作用及其相关机制。方法用MTT法测定阿霉素、EBB单独及联合用药对阿霉素杀伤乳腺癌多药耐药细胞系(MCF-7/ADR)及其亲代细胞系(MCF-7)的作用的IC50值,用不同浓度EBB处理MCF-7/ADR细胞后用FACS法分析EBB对阿霉素诱导细胞凋亡及对mdr1mRNA和P-gp蛋白水平表达的影响,通过激光共聚焦显微镜观察EBB处理前后及用EBB预处理24和48h后MCF-7/ADR和MCF-7细胞内阿霉素浓度的改变。结果MTT结果显示EBB对MCF-7和MCF-7/ADR都具有抗肿瘤活性;EBB还能协同提高阿霉素的细胞毒作用,MCF-7组两药相互作用指数(CDI)值为0.73,MCF-7/ADR组CDI值为0.49,其对耐药细胞的协同作用更为明显。随EBB剂量增加,低剂量阿霉素诱导MCF-7/ADR细胞凋亡增加而且P-gp蛋白表达水平逐渐下降,细胞内阿霉素浓度逐渐提高,而且用EBB预处理MCF-7/ADR细胞24和48h后细胞内阿霉素和罗丹明浓度也逐渐提高。结论EBB是有效的肿瘤细胞化疗药物,它不但能直接抑制P-gp功能还具有下调P-gp蛋白表达的作用,从而有效逆转MCF-7/ADR细胞的耐药现象,协同增强化疗药物对耐药细胞的杀伤作用。     

丹参酮Ⅱ_A逆转多药耐药的体外效应研究

目的:研究丹参酮ⅡA逆转多药耐药的体外效应。方法:以0[仅20 mg/L多柔比星(ADM)或顺铂(DDP),阴性对照]、5mg/ml丹参酮ⅡA(联合20 mg/L ADM或DDP)培养人乳腺癌耐ADM(MCF-7/ADM)细胞、人肺癌耐DDP(A549/DDP)细胞24、48 h后,采用MTT法测定细胞活力;聚合酶链反应(PCR)法测定细胞中细胞周期控制蛋白CDC25A、细胞周期蛋白依赖性激酶2(CKD2)m RNA表达。结果:与阴性对照比较,丹参酮ⅡA作用于MCF-7/ADM、A549/DDP细胞24、48 h后细胞活力减弱,细胞中CDC25A、CKD2 m RNA表达减弱,差异有统计学意义(P<0.01)。结论:丹参酮ⅡA联合ADM或DDP能够抑制MCF-7/ADM和A549/DDP的细胞活力,减弱细胞中CDC25A、CKD2 m RNA表达,具有一定的逆转恶性肿瘤多药耐药的作用。     

脂质体阿霉素逆转肿瘤多药耐药的活性和机制研究

目的 探讨脂质体阿霉素( PLD)逆转肿瘤多药耐药(MDR)的活性及其逆转机制.方法 以噻唑蓝(MTT)方法检测PLD对多药耐药肿瘤细胞MCF-7/ADR及KBv200的耐药逆转活性.结果 PLD在体内具有较强的逆转活性,逆转活性大于公认的强逆转剂维拉帕米的活性;在5.0μmol/L浓度下使多药耐药细胞KBv200对长春新碱的敏感性增加了45倍.PLD浓度依赖性增加(0、2.5、5.0、10 μmol/L)KBv200细胞内的罗丹明蓄积.PLD的心脏毒性、骨髓抑制以及脱发等不良反应显著降低.结论 脂质体阿霉素具有较强的逆转MDR的活性,主要通过持续向肿瘤组织聚集,肿瘤局部药物浓度升高,抗肿瘤的活性增强.     

耐药人乳腺癌细胞中葡萄糖神经酰胺合成酶的表达及意义

目的:探讨葡萄糖神经酰胺合成酶(GCS)基因在人乳腺癌细胞株(MCF-7)和耐阿霉素人乳腺癌细胞株(MCF-7/ADR)中的表达及意义。方法:采用MTT法检测阿霉素对MCF-7/ADR和MCF-7的半数抑制浓度(IC50),用不同浓度的GCS抑制剂PDMP预处理MCF-7/ADR不同时间后检测IC50;运用流式细胞术检测MCF-7及PDMP预处理MCF-7/ADR前、后GCS蛋白的表达水平;应用实时荧光定量PCR法检测MCF-7及PDMP作用前、后MCF-7/ADR中GCS基因的表达(GCSN)水平。结果:阿霉素对MCF-7/ADR和MCF-7的IC50分别为(18.95±0.54)、(0.84±0.07)μg·mL-1;MCF-7/ADR对MCF-7的耐药倍数为22.69倍,PDMP作用后阿霉素对MCF-7/ADR的IC50下降至(5.63±0.58)μg·mL-1。MCF-7/ADR中GCS蛋白及GCSN的表达均高于MCF-7(P<0.01),PDMP使MCF-7/ADR中GCSN表达水平从0.0048±0.0017下降至0.0021±0.0004。结论:GCS可能参与肿瘤耐药的发生过程,并在MCF-7/ADR多药耐药中起重要作用。     

1MTA2基因沉默对人乳腺癌MCF-7/ADR多药耐药的逆转作用

目的乳腺癌是女性中最常见的恶性肿瘤,本研究探讨MTA2对乳腺癌耐药的作用及机制。方法 CCK-8检测MCF-7/ADR和MCF-7细胞株对阿霉素的耐药情况。体外化学合成MTA2序列特异性的shRNA,经慢病毒转染人乳腺癌细胞系,Western blot检测慢病毒介导的MTA2敲减效率以及PI3K/AKT/NF-κB信号通路蛋白。Annexin V-FITC和DAPI染色检测细胞凋亡情况。结果 MCF-7/ADR细胞中MTA2表达量显著高于MCF-7细胞株,慢病毒介导的基因沉默显著的敲减了MCF-7/ADR细胞中的MTA2。敲除MTA2逆转MCF-7/ADR细胞的耐药作用并促进细胞凋亡。敲除MTA2通过抑制PI3K/AKT通路抑制下游NF-κB通路活化,并下调p-gp蛋白表达而逆转耐药性。结论敲除MTA2可以逆转MCF-7/ADR细胞的耐药作用,表明MTA2可能参与调节乳腺癌多药耐药作用。     

Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human breast cancer cell lines

1. Overexpression of glutathione S-transferases (GST) in breast cancer cells is hypothesized to be a component of the multifactorial doxorubicin-resistant phenotype. 2. We have characterized the expression of GST enzymes at the catalytic activity, protein and mRNA levels in wild-type MCF-7 (MCF-7/WT) human breast cancer cells and a line selected for resistance to doxorubicin (MCF-7/ADR), with the goal of modulating GST activity to overcome resistance. 3. The MCF-7/ADR cells were 30-65-fold more resistant to doxorubicin than the MCF-7/WT cells. 4. Total cytosolic GST catalytic activity was elevated 23-fold in the MCF-7/ADR cells as compared with the MCF-7/WT cells, and the MCF-7/ADR cells also showed 3-fold increases in catalytic activity toward GST mu and alpha class-selective substrates. Neither cell line showed detectable catalytic activity with a GST mu class-selective substrate. 5. MCF-7/ADR cells showed pronounced overexpression of GST mu protein and GST P1 mRNA in comparison with the wild-type cell line. Neither cell line displayed detectable GST alpha or mu at the protein level. 6. A glutathione analogue that functions as a selective GST alpha inhibitor was more potent at inhibiting total cytosolic GST catalytic activity in the MCF-7/ADR cell line than GST alpha and mu class-selective inhibitory glutathione analogues and the non-selective GST inhibitor ethacrynic acid. 7. The multidrug resistance-associated protein, which can function as a glutathione-conjugate transporter, appeared weakly overexpressed in the MCF-7/ADR cells in comparison with the MCF-7/WT cells.     

N-糖基取代的邻苯二甲酰亚胺新衍生物的合成与肿瘤多药耐药逆转作用研究

沙利度胺（α-N-phthalimido-glutarimide，TLD）是一种具有抗血管生成和抗炎作用的药物，对多种实体瘤有效。本文研究了N-糖基取代的沙利度胺新衍生物（STA-35）对阿霉素（doxorubicin，ADR）引起的多药耐药（multidurg resistance，MDR）的调节作用。采用SRB法检测化合物对癌细胞的增殖抑制作用，应用流式细胞术测定P-糖蛋白（P-glycoprotein，P—gp）的功能，以免疫印迹方法考察P—gP的蛋白表达。实验结果表明，STA-35能够抑制人乳腺癌细胞MCF-7及其ADR耐药细胞MCF-7／ADR生长，耐药指数仅为1．19；并能增强MCF-7／ADR细胞对ADR的敏感性。此外，STA-35可以增加MCF-7／ADR细胞内罗丹明123（rhodamine 123，RH123）的聚积，减弱P—gP的功能，抑制P-gp的蛋白表达。该化合物具有多药耐药逆转作用，其分子机制可能与抑制P—gp的功能和蛋白表达相关。     

2—ASG —3—（3‘,5’—双吗啉甲基—4‘—羟基）—苯甲酰吲哚（HWL—12）逆转肿…

AIM: To explore the reversal of multidrug resistance (MDR) by indole derivative HWL-12. METHODS: Cytotoxicity was determined by tetrazolium (MTT) assay. The function of P-gp was examined by Fura 2-AM assay. Cellular accumulation of doxorubicin (Dox) was measured by fluorescence spectrophotometry. RESULTS: HWL-12 10 mumol.L-1 markedly increased Fura-2 accumulation and was 17.2-fold reversal of MDR in MCF-7/ADR cells. The cellular Dox accumulation in MDR cells was increased in the presence of HWL-12 on the MCF-7/ADR cells. No effect was observed for Dox accumulation in the presence of high Ca2+ (addition of CaCl2) or low Ca2+ (addition of egtazic acid). CONCLUSION: HWL-12 has a potent MDR reversal action which was associated with the increase of cellular Dox accumulation in MDR cells and not related with calcium ion concentration.     

Biphasic accumulation kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile in tumour cells and its modulation by lipophilic P-glycoprotein ligands.

AIM: To study the accumulation and washout kinetics of [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) in MDR positive and MDR negative tumour cells and how this is modified by lipophilic P-glycoprotein ligands. METHODS: The tumour cells were incubated in the presence and absence of the ligands and the uptakes of 99mTc-MIBI, rhodamine 123 and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) were measured. RESULTS: The accumulation of 99mTc-MIBI in the tumour cells followed biphasic kinetics. Verapamil and cyclosporin A increased the membrane fluidity and significantly enhanced the 99mTc-MIBI uptake of the MDR negative cells, while the rhodamine 123 uptake was not affected. Verapamil significantly increased the uptake of rhodamine 123 and 18FDG but did not modify that of 99mTc-MIBI in the MDR positive cells. Cyclosporin A significantly increased the 18FDG uptake of the MDR positive and negative tumour cells; these effects were ouabain-sensitive. Depolarization of the cytoplasmic membrane, acidification of the extracellular medium and the administration of CCCP decreased the accumulation of 99mTc-MIBI and rhodamine 123 uptake in the tumour cells. CONCLUSIONS: Lipophilic P-glycoprotein ligands modified the biphasic accumulation kinetics of the 99mTc-MIBI uptakes of MDR negative and positive tumour cells in different and complex ways and could therefore mask the P-glycoprotein pump-dependent changes in tracer accumulation.     

Reversal of P-gp mediated multidrug resistance in-vitro and in-vivo by FG020318

Overexpression of P-glycoprotein (P-gp) by tumours results in multidrug resistance (MDR) to structurally and functionally unrelated chemotherapeutic drugs. Combined therapy with MDR-related cytotoxins and MDR modulators is a promising strategy to overcome clinical MDR. This study was performed to explore the MDR reversal activity of a novel compound 2-[4-(2-pyridin-2-yl-vinyl) phenyl]-4,5-bis-(4-N,N-diethylaminophenyl)-1(H)-imidazole (FG020318) in-vitro and in-vivo. Tetrazolium (MTT) assay was used to evaluate the ability of FG020318 to reverse drug resistance in two P-gp-expressing tumour cell lines, KBv200 and MCF-7/adr. Intracellular doxorubicin accumulation was determined by fluorescence spectrophotometry in MCF-7/adr cell line. The effect of FG020318 on P-gp function was demonstrated by rhodamine 123 (Rh123) accumulation in KBv200 cells. KBv200 cell xenograft models were established to study the in-vivo effect of FG020318 on reversing MDR. FG020318 was not cytotoxic by itself against P-gp expressing KBv200 cells and MCF-7/adr cells and their parental drug-sensitive KB cells and MCF-7 cells. FG020318 could significantly increase the sensitivity of MDR cells to antitumour drugs including doxorubicin and vincristine in MCF-7/adr cells and KBv200 cells, respectively. It was much stronger than the positive control verapamil in reversal of MDR. FG020318 also increased the intracellular accumulation of doxorubicin in a concentration-dependent manner in MCF-7/adr cells, but did not affect the accumulation of doxorubicin in drug-sensitive MCF-7 cells. The Rh123 accumulation in resistant KBv200 cells was also increased by the addition of FG020318, but Rh123 accumulation was not affected by FG020318 in drug-sensitive KB cells. FG020318 potentiated the antitumour activity of vincristine to KBv200 xenografts and was an efficacious modulator in-vivo. Our results suggested that FG020318 was a highly potent, efficacious MDR modulator not only in-vitro but also in-vivo. The reversal of drug resistance by FG020318 was probably related to the increased anticancer drug accumulation and its inhibition of P-gp function of MDR tumour cells.     

Role of differential drug uptake, efflux, and binding of etoposide in sensitive and resistant human tumor cell lines: implications for the mechanisms of drug resistance

In order to study the mechanism of etoposide (VP-16) resistance in human tumor cells and to assess the role of P-170 glycoprotein in VP-16 accumulation, we have examined the uptake and efflux of VP-16 in both sensitive and multidrug-resistant MCF-7 human breast and HL60 human promyelocytic leukemia cells. The drug-resistant cells, MCF-7/ADR and HL60/ADR, were selected for resistance to adriamycin and were 200- to 250-fold resistant to VP-16. Whereas MCF-7/ADR cells overexpress the P-170 glycoprotein and show the multidrug-resistant phenotype, HL60/ADR cells do not overexpress the P-170 glycoprotein. Although there was a 2-fold decrease in accumulation of VP-16 in MCF-7/ADR cells, this decrease did not correlate with a 250-fold resistance to the drug. VP-16 efflux was rapid and almost complete from MCF-7 cell lines and it was decreased at 4 degrees. Further, there was a significant increase in VP-16 accumulation in the MCF-7/ADR cells in the presence of glucose-free medium supplemented with sodium azide. However, no change in the pattern of VP-16 efflux was observed. Under these conditions, addition of glucose caused release of VP-16 from MCF-7/ADR cells, suggesting energy-dependent modifications in the drug binding. Coincubation of vincristine with VP-16 also increased the drug accumulation and decreased the rate of efflux of VP-16 in both sensitive and resistant MCF-7 cells, suggesting that vincristine and VP-16 may compete for similar binding and efflux mechanisms in these cell lines. In contrast, daunorubicin increased VP-16 accumulation only in the sensitive MCF-7 cell line, whereas the efflux rate of VP-16 was not significantly changed in either cell line. HL60 sensitive cells accumulated 4- to 5-fold more VP-16 than the resistant subline. Both sensitive and resistant cells showed an important noneffluxable pool of the drug, 3-fold larger for sensitive cells (79 +/- 12 versus 25 +/- 2 pmol of VP-16/mg of protein, for sensitive and resistant cells, respectively). The efflux of VP-16 was temperature dependent only in sensitive cells. VP-16 accumulation in HL60/ADR cells was increased in glucose-free medium supplemented with sodium azide; however, the noneffluxable pool of VP-16 was not significantly changed. In contrast, although these conditions had no effect on the drug accumulation in the parental line, they caused a decrease in the noneffluxable pool of VP-16, suggesting an energy-dependent binding and retention of VP-16.(ABSTRACT TRUNCATED AT 400 WORDS)     

Adenovirus-mediated p53 gene therapy reverses resistance of breast cancer cells to adriamycin

The aim of this study was to determine whether adenovirus-mediated p53 gene (Ad-p53) transfection can enhance adriamycin cytotoxicity and reverse adriamycin resistance in human breast cancer cells and explore its effect on the expression of MDR1 gene and permeability-glycoprotein (P-gp). Human breast cancer cell lines, MCF-7 and MCF-7/ADR, were used in in-vitro studies. After infection with Ad-p53, the cytotoxicity of adriamycin was evaluated using the Cell Counting Kit-8 assay. The expression of MDR1 mRNA was detected by quantitative real-time PCR. The expression of P-gp was analyzed using western blotting. In in-vivo studies, MCF-7/ADR tumor cells were inoculated subcutaneously in athymic nude mice. After 14 days of inoculation, tumor size was measured. Apoptosis and expression of P-gp in the tumor tissue were analyzed by fluorescence activated cell sorting and western blotting. After transfection with a multiplicity of infection of 50 for Ad-p53, chemosensitivity of MCF-7/ADR cells increased by 18.1 times (P=0.001), and 50% inhibitory concentration (IC50) of adriamycin decreased from 4.54 ± 0.91 to 0.26 ± 0.11 mg/l. Real-time PCR showed that MDR1 mRNA decreased from 1.32 to 0.85 (P=0.001). Western blotting analysis showed that P-gp also decreased. In in-vivo studies, Ad-p53 combined with adriamycin dramatically inhibited the growth of subcutaneous xenograft of MCF-7/ADR. The fluorescence activated cell sorting assay showed that there were more apoptotic cells in tumor tissues treated with Ad-p53 and adriamycin. The expression of P-gp was significantly decreased in tumor tissues. This study suggests that Ad-p53 can reverse MCF-7/MDR cell resistance to adriamycin. The reversal effect was associated with inhibition of P-gp expression and induction of apoptosis.     

Effects of miltefosine on membrane permeability and accumulation of [Tc]-hexakis-2-methoxyisobutyl isonitrile, 2-[F]fluoro-2-deoxy-d-glucose, daunorubucin and rhodamine123 in multidrug-resistant and sensitive cells

Miltefosine is a phospholipid analog that exhibits antineoplastic activity against breast cancer metastases, but its mechanism of action remains uncertain. The aim of this study was to investigate the transport mechanism for the removal of miltefosine and [99mTc]-hexakis-2-methoxyisobutyl isonitrile (99mTc-MIBI) from multidrug-resistant cells. The P-glycoprotein pump function, cell viability, and 99mTc-MIBI and 2-[18F]fluoro-2-deoxy-D-glucose (18FDG) uptakes were measured in NIH 3T3 (3T3) and NIH 3T3MDR1 G185 (3T3MDR1) mouse fibroblasts and human lymphoid B JY cells. Miltefosine treatment increased the permeability and fluidity of these tumor cells in a concentration-dependent manner. The multidrug-sensitive cells were 3-4 times more sensitive to miltefosine than the multidrug-resistant ones. The extent of 99mTc-MIBI accumulation in the P-glycoprotein-expressing cells increased in the presence of miltefosine, whereas the rhodamine123 and daunorubicin uptakes of the cells did not change significantly. In the 3T3MDR1 cells verapamil reinstated the rhodamine123 and daunorubicin accumulation, but not the 99mTc-MIBI uptake. Cyclosporin A reinstated the uptakes of 99mTc-MIBI, daunorubicin and rhodamine123 by the 3T3MDR1 cells. In a concentration-dependent manner miltefosine decreased the extents of 99mTc-MIBI, rhodamine123, daunorubicin and 18FDG accumulation in the JY and 3T3 cells. Our findings indicate a common transport mechanism for 99mTc-MIBI and miltefosine, which is distinct from that for rhodamine123 and daunorubicin in MDR cells.