MIF对耐ADM人乳腺癌细胞MCF-7/ADM体内外耐药逆转作用  

Reversal effect of mifepristone on adriamycin resistance in human breast cancer cell line MCF-7/ADM in vitro and in vivo

作　　者：黄俊辉[1] 张轶[2] 黄玉婷[3] 张曦蓓[3] 肖佳[3] 

机构地区：[1]中南大学湘雅医院肿瘤科,长沙410008 [2]湖南省肿瘤医院外科,长沙410006 [3]中南大学湘雅医学院2006级研究生班,长沙410078

出　　处：《中南大学学报（医学版）》2010年第6期576-583,共8页Journal of Central South University ：Medical Science

基　　金：湖南省中医药基金(24201)~~

摘　　要：目的:采用动物体内外结合方法探讨米非司酮(mifepristone,MIF)对耐阿霉素(adriamycin,ADM)人乳腺癌细胞MCF-7/ADM耐药逆转作用。方法:四甲基偶氮唑蓝法检测5μmol/LMIF对MCF-7/ADM体外耐药逆转作用。MCF-7/ADM接种裸鼠皮下构建裸鼠移植瘤模型,空白对照组(NS组)为0.2mL生理盐水腹腔注射+0.5mL食用油灌胃;ADM组为5mg/kgADM腹腔注射+0.5mL食用油灌胃;MIF组为30mg/kgMIF灌胃+0.2mL生理盐水腹腔注射;ADM+MIF组为5mg/kgADM腹腔注射+30mg/kgMIF灌胃。观察各组裸鼠移植瘤情况。结果:(1)5μmol/LMIF对MCF-7/ADM细胞的抑制率小于5%,与未用MIF组的抑制率比较差异无统计学意义(P>0.05)。(2)ADM对MCF-7/ADM细胞的半抑制率为17.21mg/L,而对非耐药乳腺癌细胞MCF-7细胞的半抑制率为0.42mg/L,ADM对MCF-7/ADM细胞的半抑制率明显高于MCF-7的半抑制率(P<0.05)。(3)5μmol/LMIF与ADM联合处理MCF-7/ADM细胞后,MCF-7/ADM半抑制率为1.96mg/L,明显低于单用ADM组的半抑制率(P<0.05)。逆转ADM耐药倍数为8.78。(4)ADM+MIF组瘤体积[(232.5149±309.2377)mm3]均低于NS组的瘤体积[(962.2309±261.1313)mm3](均P<0.05),也低于MIF组的瘤体积[(778.2846±42.6919)mm3],还低于ADM组的瘤体积[(508.9648±16.2609)mm3](均P<0.05)。MIF+ADM组的瘤质量抑制率为78.0%。结论:MIF对耐阿霉素的人乳腺癌细胞MCF-7/ADM体内外均有逆转耐药性的作用。Objective To explore the reversal effect of mifepristone（MIF） on adriamycin（ADM） resistance in human breast cell line MCF-7/ADM in vitro and in vivo.Methods The transplantable models of MCF-7 cells resisting against adriamycin were established in nude mice by subcutanceous implantation to observe the reversal effect of MIF in vivo.The mice were randomly divided into 4 groups：a control group（treated with saline water 0.2 mL intraperitoneally and edible oil 0.5 mL orally）,an MIF group （treated with mifepristone 30 mg/kg orally and saline water 0.2 mL intraperitoneally）,an ADM group （treated with adriamycin 5 mg/kg intraperitoneally and edible oil 0.5 mL orally） and an ADM＋MIF group （treated with ADM 5mg/kg intraperitoneally and mifepristone 30mg/kg orally every 3 days）.Tumor changes were investigated after different drug treatments.The reversal effect of 5μmol/L MIF in vitro on the ADM resistance cell line MCF-7/ADM and non ADM resistance cell line MCF-7 was determined by 4,5-dimethylthiazol-2-yl （MTT） assay.Results （1） The inhibitory rate of 5μmol/L of MIF for both cell lines MCF-7 and MCF-7/ADM was less than 5%,and it had no statistical difference compared with the group that was not treated with MIF（P0.05）.（2） ADM could inhibit the growth of both MCF-7 and MCF-7/ADM,but the inhibition concentration 50 （IC50） of MCF-7 （0.42 mg/L） was obviously less than that of MCF-7/ADM（17.21mg/L）（P0.05）.（3） IC50 of MCF-7/ADM of MIF＋ADM group was 1.96 mg/L in vitro,which was significantly less than that in ADM alone group（17.21 mg/L）（P0.05）,and 5μmol/L of MIF reversed ADM resistance with fold-reversal of 8.78.（4） MIF had some effect on the inhibition of MCF-7/ADM cell growth in vivo,the xenograft volume in the MIF＋ADM group [（232.5149±309.2377）mm3] was significantly smaller than that in the control group[（962.2309±261.1313） mm3 ] after the 4 week treatment（P0.05）,and also smaller than that in the MIF group [（778.2846±42.6919）mm3

关 键 词：米非司酮 阿霉素 耐阿霉素人乳腺癌细胞株MCF-7 逆转 多药耐药 

分 类 号：R737.9[医药卫生—肿瘤]