项目名称: 核仁素(NCL)与miR-221相互作用调控急性白血病耐药的研究
项目编号: No.81470326
项目类型: 面上项目
立项/批准年度: 2015
项目学科: 医药、卫生
项目作者: 胡建达
作者单位: 福建医科大学
项目金额: 70万元
中文摘要: 成人急性白血病(AL)复发率高,5年总生存率(OS)较低,对化疗药物产生耐药是AL治疗失败的主要原因之一。前期的预实验结果显示,核仁素(NCL)及miR-221在耐药的白血病细胞株高表达,并且复发/难治患者的阳性率也明显高于初治患者,两者间的表达呈一定程度的相关性,NCL与miR-221如何相互作用?如何影响白血病的耐药性?目前均未明了。本项目拟从患者表达水平检测、细胞体外实验及动物体内实验三大方面进行研究,采用干扰及过表达技术,以HL-60细胞及耐阿霉素的HL-60细胞(HL-60/ADR)、Molt-4及其耐阿霉素的细胞(MAR)为研究对象,观察上调/下调NCL基因及miR-221对白血病细胞耐药表型的影响,将从新的角度探讨NCL及miR-221的相互作用对白血病耐药的影响及其分子机制。为指导AL分层治疗,疗效监测、预后判断,具有重要的临床实际意义和应用价值。
中文关键词: miR-221;核仁素;急性白血病;耐药;分子机制
英文摘要: Adult acute leukemia (AL) have higher relapsed rate and lower 5-year overall survival (OS). Preliminary experimental results showed that nucleolin (NCL) and miR-221 were over-expressed in resistant leukemic cell lines. Refractory or relapsed AL patients had higher positivity of miR-221 and NCL expression than newly diagnosed patients, but the exact mechanism is not yet clear. The project were be carried out from three aspects: to detect NCL/ miR-221 expression levels in AL patients, experimental studies of cell lines in vitro and of NOD/SCID mice xenograft in vivo. The project intends to use RNA interference and over-expression technology, to observe resistant phenotypes of AL cells by up-regulation/down-regulation NCL/ miR-221 in HL-60 and adriamycin-resistant HL-60 cell (HL-60/ADR)、Molt-4 and adriamycin-resistant Molt-4(MAR). The interaction between NCL and miR-221 and its involvement in drug resistance was aiso investigated. It would provide a new clue for monitoring the drug resistance and evaluating prognosis in AL.
英文关键词: miR-221;nucleolin;acute leukemia;dug resistance;molecular mechanisms