小干扰RNA逆转人乳腺癌移植瘤多药耐药的在体研究
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庄晓明E-mail:zxmzagzj@sina.com

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南京医学科技发展项目(ZKM06056)。


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

    Abstract:

    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 MRP mRNA 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 MRP mRNA 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 MRP mRNA 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.

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庄晓明| 肖红| 武卓| 翟青新.小干扰RNA逆转人乳腺癌移植瘤多药耐药的在体研究[J].中国普通外科杂志,2010,19(5):501-505.
DOI:10.7659/j. issn.1005-6947.2010.05.012

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  • 收稿日期:2009-10-14
  • 最后修改日期:2010-04-28
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  • 在线发布日期: 2010-05-15