Ku80 RNAi技术增强肺癌放射敏感性的动物实验研究

[目的]探讨在Ku80 mRNA双链小RNA片段有效抑制A549肺癌细胞Ku80表达的基础上联合放疗增强肿瘤组织放射敏感性的可行性。[方法]体外培养A549肺癌细胞,并制备BALB/c裸鼠实体瘤模型,用Ku80 siRNA转染肿瘤组织。用免疫组织化学法测定转染Ku80 siRN A48h后肿瘤组织内Ku80蛋白表达情况。Ku80 siRNA转染BALB/c裸鼠实体瘤48h后进行局部射线照射10Gy。隔日测量一次肿瘤体积,共观察20d,绘制肿瘤生长曲线,观察肿瘤体积、相对生长速率和生长抑制率。[结果]转染Ku80 siRNA后移植瘤内Ku80蛋白表达量较各对照组减少（P〈0.05）,而且转染Ku80 siRNA并联合射线照射组的肿瘤体积、相对生长速率和生长抑制率与各对照组比较,差异均有统计学意义（P=0.000）。[结论]转染Ku80 siRNA后A549肺癌细胞Ku80蛋白表达下调,放射敏感性增强。

An Animal Study on Enhancing Radiosensitivity of Lung Cancer with Ku80 RNAi Technique

[Purpose] To investigate whether silencing Ku80 gene by siRNA technique can effective- ly enhance the radiosensitivity of A549 lung cancer cells. [Methods] Lung cancer cells A549 were cultured in vitro, and implanted it into BALB/c nude mice to make xenografts models. The xenografts were transfected with Ku80 siRNA. Ku80 protein expression in xenograft was determined by immunohistochemistry after 48h transfection with Ku80 siRNA. The xenografts were locally irradiated with a single dose of 10Gy after 48h transfection with Ku80 siRNA. Tumor volume was measured every other day for 20 days, and tumor growth curves were drawn. The xenograft volume, relative growing rate and growing inhibiting rate were observed. [Results] Ku80 protein in Ku80 siRNA transfected group was significantly reduced than that in control groups （P〈0.05）. The xenograft volume, relative growing rate and growing inhibiting rate of the xenografts in Ku80 siRNA transfected group were statistically different comparing with those in other groups（P=0.000）. [Conclusion] Down- regulated expression of Ku80 protein in lung cancer cells A549 xenografts after transfection with Ku80 siRNA can effectively enhance the radiosensitivity.