RNA interference-triggered reversal of ABCC2-dependent cisplatin resistance in human cancer cells
RNA interference-triggered reversal of ABCC2-dependent cisplatin resistance in human cancer cells
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DOI：
10.1016/j.bbrc.2006.07.022
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发表时间：
2006-09-15
影响因子：
3.1
通讯作者：
Lage, Hermann
中科院分区：
文献类型：
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作者：
Materna, Verena;Stege, Alexandra;Lage, Hermann
三磷酸腺苷结合盒（ABC）转运蛋白ABCC 2（MRP 2/cMOAT）可介导对常用抗癌药物顺铂和紫杉醇的耐药性。为了克服ABCC 2依赖性耐药，设计了两种特异性的抗ABCC 2小干扰RNA（siRNA），用于瞬时触发人卵巢癌顺铂耐药细胞系A278 ORCIS中的基因沉默RNA干扰（RNAi）途径。由于两种siRNA均显示生物活性，为了稳定抑制ABCC 2，设计了相应的短发夹RNA（shRNA）编码表达载体。通过用该构建体处理A278 ORCIS细胞，靶向ABCC 2编码mRNA和转运蛋白的表达被抑制。这些作用伴随着对顺铂和紫杉醇的耐药性逆转。因此，这些数据证明了所分析的RNA作为强大的实验室工具的实用性，并表明siRNA和shRNA介导的基于RNAi的基因治疗方法可能适用于预防和逆转ABCC 2依赖性耐药性。(c)2006年爱思唯尔公司All rights reserved.
The adenosine triphosphate binding cassette (ABC)-transporter ABCC2 (MRP2/cMOAT) can mediate resistance against the commonly used anticancer drugs cisplatin and paclitaxel. To overcome the ABCC2-depending drug resistance, two specific anti-ABCC2 small interfering RNAs (siRNAs) were designed for transient triggering of the gene-silencing RNA interference (RNAi) pathway in the cisplatin-resistant human ovarian carcinoma cell line A278ORCIS. Since both siRNAs showed biological activity, for stable inhibition of ABCC2 a corresponding short hairpin RNA (shRNA)-encoding expression vector was designed. By treatment of A278ORCIS cells with this construct, the expressions of the targeted ABCC2 encoding mRNA and transport protein were inhibited. These effects were accompanied by reversal of resistance against cisplatin and paclitaxel. Thus, the data demonstrate the utility of the analyzed RNAs as powerful laboratory tools and indicate that siRNA- and shRNA-mediated RNAi-based gene therapeutic approaches may be applicable in preventing and reversing ABCC2-depending drug resistance. (c) 2006 Elsevier Inc. All rights reserved.