脉冲磁场逆转乳腺癌细胞多药耐药性的作用研究  

Reversal Effects of Pulsed Magnetic Fields on Breast Cancer Cell Line MCF-7/ADR in Vitro and in Vivo

作　　者：张翠宁[1] 刘晓秋[1] 韩英[1] 赵阿津[1] 宋保民[1] 

机构地区：[1]北京协和医学院中国医学科学院放射医学研究所,天津市300192

出　　处：《中国肿瘤临床》2008年第21期1241-1243,共3页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金资助(编号:30570437)~~

摘　　要：MTT目实的验:方研法究,脉分冲别磁检场测(不Pu同lse频dM率a及gn不eti同cF磁iel场ds强,P度MF条)对件乳照腺射癌下耐的药MC细F胞-7株/ADMRC细F-胞7/A的D耐R药的倍逆数转和作逆用转。倍方数。用流式细胞术检测经脉冲磁场照射后MCF-7/ADR细胞中Rh123药物蓄积量变化。用流式免疫荧光技术检测膜经脉冲磁场照射后MCF-7/ADR细胞膜表面P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP1)表达情况。采用半定量RT-PCR(逆转录-聚合酶链反应)检测经脉冲磁场照射后MCF-7/ADR细胞中MDR1和MRP1基因表达情况。建立人乳腺癌耐药细胞株MCF-7/ADR裸鼠移植瘤模型,通过测量肿瘤体积及重量观察PMF对肿瘤细胞的体内逆转4作0m用T。照结射果条:件脉逆冲转磁效场果能最有好效,逆可转达乳5倍腺左癌右耐;药脉细冲胞磁株场M能C提F-高7/A罗D丹R明对1阿23霉在素细产胞生内的的耐蓄药积性量(,P其<0中.011)1,0其Hz中,4101m0TH照z,M射R条P1件蛋下白可表有达效量提变升化2不0%明左显右;编药码物上蓄述积两量种;细耐胞药经蛋脉白冲的磁耐场药照基射因后表,达膜量表均面明耐显药下蛋降白;此P糖外蛋,脉白冲表磁达场量联明合显阿下霉降素,可有效关逆键转词裸鼠脉移冲植磁瘤场(的P生M长F)增值M(CPF<-07./0A1D)R。结多论药:P耐M药F具有裸逆鼠转体MD外R和1体M内R乳P1腺癌细胞多药耐药性的作用。Objective： To investigate the optimal frequency and intensity of Pulsed Magnetic Fields （PMF） in reversing multi-drug resistance in breast cancer cell line MCF-7/ADR both in vitro and in vivo. Methods： MCF-7/ADR cells were exposed to PMF of different frequencies （110 Hz and 250 Hz） and intensities （40 mT and 10 mT） for 2 hours. The concentration inhibiting growth by 50% （IC50） was determined by MTT sensitivity assay. The resistance index was calculated by dividing the IC50 of the resistant cell line MCF-7/ADR by that of the parental cell line MCF-7. The reversal index was calculated by dividing the IC50 of the resistant cell line MCF-7/ADR after treatment with PMF by that of the resistant cell line MCF-7/ADR. Cells treated with PMF and untreated cells were incubated in rhodamine123 （Rh123） solution for 2 hours at 37℃ and the intracellular accumulation of Rh123 was detected by flow cytometry. Energy-dependent efflux proteins that pump a variety of chemotherapeutic agents from tumor cells such as P-glycoprotein （p-gp） and multidrug resistance-associated protein （mrpl） on the cell membrane were evaluated by flow immunofluorescence. We used semiquantitative PCR （RT-PCR） to detect the expression of MDR1 and MRP1 mRNA and to determine the effect of PMF on the expression of multi-drug resistance genes. An MCF-7/ADR cell xenograft model was established in nude mice. The tumor volume and weight were measured to observe the effect of PMF in vivo. Results： PMF effectively reversed the adriamycin resistance of MCF-7/ADR cells （P〈0.01）, with a maximum five-fold effect using 110 Hz and 40 mT. PMF increased the intracellular accumulation of Rh123 by 20% and increased the quantity of p-gp on the cell membrane. PMF had little effect on mrpl mRNA but decreased the expression of MDR1 and MRP1 proteins. PMF combined with ADR inhibited tumor proliferation in our xenograft model （P〈 0.01）. Conclusion： PMF decreases MDR1 and MRP1 gene expression in the MCF-7/ADR breast cancer cell l

关 键 词：脉冲磁场(PMF) MCF-7/ADR 多药耐药 裸鼠 MDR1 MRP1 

分 类 号：R737.9[医药卫生—肿瘤]