权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Study on twnor growth inhibition by small interference RNAin nude mice

小干扰RNA抑制裸鼠双胞胎生长的研究

基本信息

批准号：
18591389
负责人：
OHNISHI Ken
金额：
$ 2.37万
依托单位：
Nara Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591389/
关键词：
radiation apoptosis cell death signal transduction cell survival signal transduction DNA-repair cell survival sensitization RNA干渉 siRNA 担がんマウス腫瘍増殖抑制

项目摘要

Interference with anti-apoptosis and/or cellular proliferation signal transduction is regarded to result in effective radiation cancer therapy. This study examined the effectiveness of siRNA targeting key factors (NBS1 and XIAP) in DNA repair and signal transduction for anti-apoptosis and/or cellular proliferation after radiation using cultured human cancer cells and tumor-transplanted nude mica Radiation sensitivity and apoptosis were analyzed with colony formation assay, Western blot, fluorescent immuno-cytochemistry and hoechst staining using wild-type p53 or mutated p53 gene-transfected human lung and tongue cancer cells. Further the cancer cells were transfected with plasmids which were inserted with NBS1-siRNA expressing DNA cassette and radiation, sensitivity of the plasmid-transfected cells was examined. siRNAs targeting NBS1 and XIAP enhanced radiation sensitivity p53 independently and even more pronounced in mutated p53 cells compared with wild-type p53 cells. Enhanced radiation sensitivity was not observed in several clones from NBS1-siRNA expressing plasmid-transfected cells at this time. Our results suggest that t NBS1-siRNA and XIAP siRNA might contribute to high curative efficiency in radiation cancer therapy for malignant cancer leading to enhanced p53 independent radiation sensitivity. In addition, it was suggested that further experiments are required for study on the effectiveness of siRNAs in vivo system.

干扰抗细胞凋亡和/或细胞增殖信号转导被认为是有效的放射治疗癌症的结果。本研究以体外培养的人肺癌细胞为研究对象，研究了针对关键因子(NBS1和XIAP)的siRNA在辐射后DNA修复和抗细胞凋亡和/或细胞增殖的信号转导中的作用，并以野生型和突变型p53基因转染人肺癌和舌癌细胞为研究对象，用克隆形成实验、Western印迹、荧光免疫细胞化学和Hoechst染色等方法分析了siRNA对辐射敏感性和细胞凋亡的影响。进一步将含有表达DNA盒和辐射的NBS1-siRNA的质粒导入癌细胞，检测其对辐射的敏感性。针对NBS1和XIAP的siRNA独立地增强了p53的辐射敏感性，与野生型p53细胞相比，突变的p53细胞中的siRNA更加明显。目前，从NBS1-siRNA表达质粒的细胞中未观察到几个克隆的辐射敏感性增强。我们的结果提示，t NBS1-siRNA和XIAP siRNA可能有助于恶性肿瘤放射治疗的高疗效，从而增强P53非依赖的辐射敏感性。此外，对siRNAs在体内系统的有效性还需要进一步的实验研究。