采用病毒载体介导的RNAi同时抑制XIAP和survivin表达对胰腺癌放化疗敏感性的研究

项目名称： 采用病毒载体介导的RNAi同时抑制XIAP和survivin表达对胰腺癌放化疗敏感性的研究

项目编号： No.30872492

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 李宜雄

作者单位： 中南大学

项目金额： 30万元

中文摘要： 胰腺癌是一种常见的恶性肿瘤，其发病率和死亡率国内外均有增加的趋势。其发病隐匿，发现时往往已是晚期，仅10%－20%的患者适合手术治疗。而胰腺癌对化疗和放疗敏感性差，导致其5年生存率仅为4%左右。研究表明，胰腺癌对化疗和放疗敏感性差的共同机制为癌细胞凋亡受抑；而作用最强的两种凋亡抑制基因XIAP和survivin在胰腺癌中的高表达，是胰腺癌细胞对化疗和放疗敏感性差的重要机制；同时抑制两者表达可能对改善胰腺癌的放化疗敏感性有重要意义。以前国内外的研究中，同时抑制两种基因的方法都存在一定的缺陷，少有同时抑制XIAP和Survivin两种基因的报道。逆转录病毒介导的RNA干扰可以同时实现两种基因高效特异的抑制效果。本研究我们拟采用这种方法，同时抑制胰腺癌中的XIAP和survivin两种基因，希望能克服以前研究的不足，为胰腺癌基因治疗提供新的方法和靶点，从而实现改善胰腺癌预后的最终目的

中文关键词： 胰腺癌；RNA干扰；XIAP； Survivin

英文摘要： Pancreatic cancer is a common malignant tumor,of which the mobidity and motality is getting higher every year both in our country and at abroad . Due to the asymptomatic onset of pancreatic cancer, most patients are in advanced or metastatic condition at the time of diagnosis and only 10%-20% of them are resectable.The pantients' overall 5-year survival rate is only around 4% because pancreatic cancer are resistant to radiography and chemothrophy.The studies demonstrate that the mechanism of the resistance to radiography and chemotheraphy is inhibtion to apoptosis of cancer cell.XIAP and survivin which are the most important genes in IAPs are overexpressed in pancreatic cancer and they are thought to be the improtant mechanism contributed to the resistance to radiography and chemotherophy of pancreatic cancer. Simutaneous inhibition XIAP and survivin may have an significance in impproving the sensitivity to radiography and chempthraphy of pancreatic cancer.There are disadvantages in the methods of simutaneous inhibition of the two genes, which are used in previous studies in our country and at abroad.There are few reports about the simutaneous inhibition of XIAP and survivin .Reverse transcription mediated RNAi can simutaneous inhibit both XIAP and survivin in a sufficent and specitic way.In the present study,we are going to simutaneously inhibit XIAP and survivin by using this method in the hope of impproving the diadvantage of the previous study and providing new target of gene theropy in pancreatic cancer,so that we can finally improve the prognosis of pancreatic cancer

英文关键词： pancreatic cancer; RNAi; XIAP;survivin