Study on twnor growth inhibition by small interference RNAin nude mice

干扰抗凋亡和/或细胞增殖信号转导被认为是导致有效的放射治疗癌症。本研究利用培养的人癌细胞和移植的裸骨mica检测siRNA靶向DNA修复和信号转导中关键因子（NBS1和XIAP）在辐射后抗凋亡和/或细胞增殖中的作用，采用集落形成实验、Western blot、荧光免疫细胞化学和hoechst染色分析野生型p53或突变p53基因转染的人肺癌和舌癌细胞的辐射敏感性和凋亡情况。然后用转染了表达DNA盒的NBS1-siRNA的质粒转染癌细胞并进行辐射，检测转染的质粒对癌细胞的敏感性。与野生型p53细胞相比，靶向NBS1和XIAP的sirna在突变型p53细胞中单独增强了p53的辐射敏感性，甚至更为明显。目前，在表达质粒转染的NBS1-siRNA细胞的几个克隆中没有观察到增强的辐射敏感性。我们的研究结果表明，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独立的放射敏感性。此外，还需要进一步的实验来研究sirna在体内系统中的有效性。

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.