小干扰RNA逆转人乳腺癌移植瘤多药耐药的在体研究  

The reversal effecy of siRNA on multidrug resistance of xenotsgraft human breast cancer tumor

作　　者：庄晓明[1] 肖红[2] 武卓[2] 翟青新[3] 

机构地区：[1]南京大学医学院附属鼓楼医院普通外科,江苏南京210008 [2]南京医科大学附属脑科医院研究所,江苏南京210029 [3]南京大学医学院附属鼓楼医院动物实验中心,江苏南京210008

出　　处：《中国普通外科杂志》2010年第5期501-505,共5页China Journal of General Surgery

基　　金：南京医学科技发展项目(ZKM06056)

摘　　要：目的探讨以多药耐药相关蛋白(MRP)为靶标的小干扰RNA(siRNA)抑制相应基因的表达,观察其对裸鼠人乳腺癌移植瘤化疗敏感性的影响。方法将以MRP基因为靶标的siRNA电穿孔转入裸鼠人乳腺癌模型中,用RT-PCR方法和免疫组化法检测乳癌组织MRP mRNA和蛋白的表达水平,并检测乳腺癌组织对抗肿瘤药物的敏感性。结果 RT-PCR显示转染siRNA 24 h后MRP mRNA表达降低,为空白对照组的(63.7±8.9)%,两者差异有统计学意义(P<0.05);免疫组化检测显示siR-NA转染移植瘤48 h后,MRP蛋白的表达降低,为空白对照组的(54.3±6.4)%,两者差异有统计学意义(P<0.05);经MRPsiRNA转染后,表柔比星的抑瘤率为42.2%,而空白转染组的表柔比星抑瘤率仅为11.9%(P<0.05)。结论以MRP基因为靶标的siRNA能抑制裸鼠人乳腺癌移植瘤中MRP mR-NA和MRP蛋白的表达,从而使移植瘤对化疗药物表柔比星的敏感性明显增加,部分逆转了肿瘤的多药耐药性。Objective To study the reversal effecy of small interfering RNA（siRNA） on multidrug resistance and chemotherpy sensitivity of xenografts human breast cancer tumor,and chemotherpy sensitivity in nude mice.Methods siRNA targeted on multidrug resistance protein（MRP） was transfected into MCF-7 cell xenografts tumors of mice,then the expression level of the MRPmRNA and protein was determined,and the chemotherapeutic sensitivity of the breast cancer tissues was evaluated.Results The RT-PCR and immunohistochemistry results showed that the level of MRPmRNA and protein decreased in the experimental group 24 h after the siRNA was transfected（P〈0.05）.The tumor inhibitory rate of epirubicin was significantly increased in the siRNA transfection group compared to the control group（42.2% vs.11.9%）.Conclusions siRNA targets to MRP gene can inhibit the expression of MRPmRNA and protein in xenograft breast cancer in nude mice,results in the txenograft tumor sensitivity to epirubicin is obviously increase,and the multidrug resistance of tumor is reversed partially.

关 键 词：乳腺肿瘤 小干扰RNA 耐药相关蛋白 多药耐药 

分 类 号：R737.9[医药卫生—肿瘤]