Kinesin spindle protein SiRNA slows tumor progression
Kinesin spindle protein SiRNA slows tumor progression
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DOI：
10.1002/jcp.24103
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发表时间：
2013-01-01
影响因子：
5.6
通讯作者：
Aurisicchio, Luigi
中科院分区：
文献类型：
--
作者：
Marra, Emanuele;Palombo, Fabio;Aurisicchio, Luigi
驱动蛋白纺锤体蛋白（KSP）是微管马达驱动蛋白超家族的成员之一，在有丝分裂中起着重要的作用，它介导中心体的分离和双极纺锤体的组装和维持。KSP功能的抑制导致在有丝分裂时细胞周期停滞，形成单星微管阵列，并最终导致细胞死亡。几种KSP抑制剂目前正在临床试验中进行研究，并为开发新型抗癌疗法提供了新的机会。RNA干扰（RNAi）可能是干扰癌症相关关键分子通路的有力策略。在这项研究中，我们已经建立了一种有效的方法，用于肿瘤内递送siRNA。我们评估了靶向荧光素酶的短干扰RNA（siRNA）双链体作为替代标记物或KSP序列。为了检查RNAi治疗的潜在可行性，通过RNA治疗剂的肿瘤内电转移（IERT）将siRNA转染到预先建立的病变中。该技术允许核酸的细胞渗透并有效地敲低基因表达，尽管是瞬时的。KSP特异性siRNA显著减少皮下黑色素瘤和卵巢癌病变的生长。我们的研究结果表明，瘤内电转移siRNA是可行的，KSP特异性siRNA可能为治疗干预提供一种新的策略。J.细胞。228：5864，2013。(c)2012 Wiley Periodicals，Inc.
The kinesin spindle protein (KSP), a member of the kinesin superfamily of microtubule-based motors, plays a critical role in mitosis as it mediates centrosome separation and bipolar spindle assembly and maintenance. Inhibition of KSP function leads to cell cycle arrest at mitosis with the formation of monoastral microtubule arrays, and ultimately, to cell death. Several KSP inhibitors are currently being studied in clinical trials and provide new opportunities for the development of novel anticancer therapeutics. RNA interference (RNAi) may represent a powerful strategy to interfere with key molecular pathways involved in cancer. In this study, we have established an efficient method for intratumoral delivery of siRNA. We evaluated short interfering RNA (siRNA) duplexes targeting luciferase as surrogate marker or KSP sequence. To examine the potential feasibility of RNAi therapy, the siRNA was transfected into pre-established lesions by means of intratumor electro-transfer of RNA therapeutics (IERT). This technology allowed cell permeation of the nucleic acids and to efficiently knock down gene expression, albeit transiently. The KSP-specific siRNA drastically reduced outgrowth of subcutaneous melanoma and ovarian cancer lesions. Our results show that intratumoral electro-transfer of siRNA is feasible and KSP-specific siRNA may provide a novel strategy for therapeutic intervention. J. Cell. Physiol. 228: 5864, 2013. (c) 2012 Wiley Periodicals, Inc.