Eg5在肾癌进展中的作用及靶向抑制Eg5治疗耐药性肾癌的效果和机制

项目名称： Eg5在肾癌进展中的作用及靶向抑制Eg5治疗耐药性肾癌的效果和机制

项目编号： No.81202017

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 丁森泰

作者单位： 山东大学

项目金额： 23万元

中文摘要： 肾癌是致死率最高的泌尿系肿瘤，对放化疗均不敏感，甚至对现有靶向治疗也已出现耐药，并因术后复发、转移率高而预后很差。有丝分裂驱动蛋白Eg5在细胞增殖中起关键作用，已成为抗癌靶向治疗的研究热点，既有研究发现Eg5与肿瘤发生、进展及预后密切相关，我们的前期研究也对此给与了印证。但Eg5在肾癌进展即增殖、迁徙及侵袭中的调控作用仍不明确，迄今也没有靶向抑制Eg5治疗肾癌的报道。因此，本课题拟通过多种实验技术证实Eg5在肾癌进展中的作用并探讨其信号传导调控机制，阐明小分子靶向抑制剂及siRNA抑制Eg5功能治疗肾癌的效果和机制。通过建立现有靶向药物耐药肾癌动物模型，首次探讨靶向抑制Eg5治疗耐药肾癌的效果。此外，研究还通过分析临床肾癌患者资料，进一步探讨Eg5表达与肾癌临床进展、术后预后之间的关系。希望为肾癌进展机制以及靶向治疗提供新的有效理论依据，最终为晚期肾癌患者提供新的治疗思路和更好预后。

中文关键词： 纺锤体驱动蛋白（Eg5）；肾癌；靶向治疗；预后；进展

英文摘要： Renal cell carcinoma (RCC) is the leading cause of death in urogenital malignancies, and RCC is resistant to chemotherapy and radiotherapy and even the existing targeted therapy. Thus, the prognosis for patients with RCC is dismal because of high recurrence and metastasis. In addition, the mechanism of RCC progression is unclear. The mitotic kinesin Eg5, known as kinesin spindle protein (KSP), which plays a critical role in the bipolar spindle formation and separation of duplicated chromosome during the early phase of mitosis, has been identified as an attractive anticancer target. Present studies show that Eg5 is closely related to tumor formation, progression and prognosis. Moreover, our previous studies confirmed that. Nonetheless, the regulatory mechanism of Eg5 on tumor proliferation, metastasis and invasion is rarely understood. And no study is reported on targeted Eg5 inhibition on RCC to date. Thus, the present study is to explore the role of Eg5 in RCC progression and clarify its regulatory mechanism by several experiment skills, and elucidate the therapeutic effect and mechanism of siRNA interfere and Eg5 inhibitors on RCC treatment. It's the first time to examine the therapeutic effect of Eg5 inhibitors in vivo by establishing the drug-resistance RCC animal model in the present study. Additionally,

英文关键词： kinesin spindle protein(Eg5)；renal cell carcinoma(RCC)；targeted therapy；prognosis；progression