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MIF对耐ADM人乳腺癌细胞MCF-7/ADM 体内外耐药逆转作用
引用本文:黄俊辉,张轶,黄玉婷,张曦蓓,肖佳.MIF对耐ADM人乳腺癌细胞MCF-7/ADM 体内外耐药逆转作用[J].中南大学学报(医学版),2010,35(6):576.
作者姓名:黄俊辉  张轶  黄玉婷  张曦蓓  肖佳
作者单位: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
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5 μmol/L MIF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0.2 mL生理盐水腹腔注射+0.5 mL食用油灌胃;ADM组为5 mg/kg ADM腹腔注射+0.5 mL食用油灌胃;MIF组为30 mg/kg MIF灌胃+0.2 mL生理盐水腹腔注射;ADM+MIF组为5 mg/kg ADM腹腔注射+30 mg/kg MIF灌胃。观察各组裸鼠移植瘤情况。结果:(1)5 μmol/L MIF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17.21 mg/L,而对非耐药乳腺癌细胞MCF-7细胞的半抑制率为0.42 mg/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)5 μmol/L MIF与ADM联合处理MCF-7/ADM细胞后,MCF-7/ADM半抑制率为1.96 mg/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。

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  

Reversal effect of mifepristone on adriamycin resistance in human breast cancer cell line MCF-7/ADM in vitro and in vivo
HUANG Junhui,ZHANG Yi,HUANG Yuting,ZHANG Xibei,XIAO Jia.Reversal effect of mifepristone on adriamycin resistance in human breast cancer cell line MCF-7/ADM in vitro and in vivo[J].Journal of Central South University (Medical Sciences)Journal of Central South University (Medical Sciences),2010,35(6):576.
Authors:HUANG Junhui  ZHANG Yi  HUANG Yuting  ZHANG Xibei  XIAO Jia
Institution:1.Department of Oncology, Xiangya Hospital, Central South University, Changsha  410008; 2.Department
of Surgery, Tumor Hospital of Hunan, Changsha 410006; 3.Postgraduates of Grade 2006
 Xiangya School of Medicine, Central South University, Changsha 410078, China
Abstract:ObjectiveTo explore the reversal effect of mifepristone(MIF) on adriamycin(ADM) resistance in human breast cell line MCF-7/ADM in vitro and in vivo. MethodsThe 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(P>0.05). (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)(P<0.05). (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)(P<0.05), 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(P<0.05), and also smaller than that in the MIF group [(778.2846±42.6919)mm3] and in the ADM group [(508.9648±16.2609) mm3](P<0.05). There was significant inhibition on xenograft weight after MIF combined with ADM treatment in vivo, and the inhibitory rate was 78.0%. ConclusionMIF can effectively reverse ADM resistance in human breast cancer cell line MCF-7/ADM both in vitro and in vivo.
Keywords:mifepristone  adriamycin  adriamycin resistance in human breast carcinoma cell line MCF-7  reverse  multidrug resistance  
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