杨琰;卢实;钟俊;李敏芳;王泽华;

• 1:广东医学院第二临床学院妇产科
• 2:华中科技大学同济医学院附属协和医院妇产科

摘要(Abstract)：

目的:研究叶酸受体-α(folic acid receptor-α,FR-α)在卵巢癌多药耐药细胞株中的表达水平,并探讨FR-α靶向的MDR1小干扰RNA(siRNA)纳米粒对卵巢癌多药耐药细胞的逆转效果。方法:采用体外浓度梯度递增法建立卵巢癌紫杉醇耐药细胞株SKOV3-ts,应用激光共聚焦法检测FR-α的表达水平。复凝聚法将叶酸修饰壳聚糖载体包裹靶向MDR1的PGPU6/GFP/Neo/PshRNA真核表达质粒(PshRNA-MDR1),形成叶酸修饰壳聚糖PshRNA-MDR1纳米粒(FA-CS-PshRNA)。采用RT-PCR、Western blot检测叶酸修饰前后,纳米粒转染细胞后MDR1 mRNA及蛋白的表达,MTT法检测SKOV3-ts半数抑制浓度(IC50)的变化。结果:激光共聚焦法显示,耐药细胞株SKOV3-ts胞膜层有FR-α强表达,经叶酸修饰后,FA-CS-PshRNA纳米粒较CS-PshRNA能更有效降低靶细胞SK-OV3-ts的靶基因MDR1 mRNA和P-gp蛋白表达(P<0.01),并逆转SKOV3-ts细胞针对紫杉醇的IC50(0.3830±0.0096 vs 0.0353±0.0006,P<0.01)。结论:经FR-α介导,FA-CS-PshRNA能更有效敲除MDR1的表达,靶向逆转卵巢癌多药耐药。

关键词(KeyWords)： 叶酸受体-α(FR-α);多药耐药基因1(MDR1);壳聚糖;卵巢肿瘤;多药耐药

Abstract:

Keywords:

基金项目(Foundation): 广东医学院博士启动基金(No:B2009011);; 广东省医学科学技术研究基金(No:B2010247)

作者(Authors): 杨琰;卢实;钟俊;李敏芳;王泽华;

DOI: 10.13283/j.cnki.xdfckjz.2011.09.006

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