Objective To investigate the influence of suppressing Skp2 gene expression on growth of lung cancer xenografts and Skp2, p27, p21 protein expression in xenografts. Methods BALB/c nude mice were injected subcutaneously with SPC⁃A⁃1 cells transfected with Skp2 shRNA 1,Skp2 shRNA 2 and Skp2 shRNA HK to construct nude mice of lung cancer animal models. Time of tumor formation and volume of tumors were observed. The mice were sacrificed and xenografts tissues were taken, and tumor inhibition rate was caculated. Protein expression of Skp2,p27, p21 in xenografts tissues was detected by Western blotting method. Results Com⁃pared with the control group and Skp2 shRNA HK group, tumor growth were inhibited and tumor volume reduced significantly in Skp2 shRNA 1 and Skp2 shRNA 2 groups. Tumor inhibition rate of Skp2 shRNA 1 and Skp2 shRNA 2 groups were(69�2±5�6)% and(64�5 ±6�1)%; expression of Skp2 protein were reduced(73�5±4�2)%, and(67�3±3�2)%; expression of p27 protein were increased (63�6± 2�2)% and(57�3±2�4)%;expression of p21 protein were increased(54�6 ±3�4)% and(51�7± 3�1)%. Conclusion In⁃hibiting the expression of Skp2 gene can significantly suppress the growth of transplanted tumor, Skp2 is expected to become a target for gene therapy of lung cancer in future.%目的：探讨抑制Skp2基因表达对裸鼠肺癌移植瘤生长以及移植瘤组织中Skp2、p27、p21蛋白表达的影响。方法构建抑制Skp2基因表达的重组质粒Skp2 shRNA 1和Skp2 shRNA 2，以及Skp2 shRNA HK重组质粒（阴性pGensil⁃HK对照质粒）。3种重组质粒分别转染肺癌SPC⁃A⁃1细胞，提取该细胞悬液于裸鼠皮下注射建立肺癌转染细胞裸鼠动物模型。观察肿瘤形成时间，测量其体积，绘制肿瘤生长曲线。裸鼠接种转染肺癌细胞30天后处死，提取移植瘤组织并计算抑瘤率， Western blotting检测移植瘤组织中Skp2、p27、p21蛋白的表达。结果转染Skp2 shRNA 1和Skp2 shRNA 2质粒的裸鼠肿瘤生长明显减慢。与对照组和Skp2 shRNA HK组比较，Skp2 shRNA 1和Skp2 shRNA 2质粒组肿瘤体积明显缩小（ P＜0�05），抑瘤率分别为（69�2±5�6）％和（64�5±6�1）％。与对照组比较， Skp2 shRNA 1和Skp2 shRNA 2质粒组Skp2蛋白下调率为（73�5±4�2）％、（67�3±3�2）％， p27蛋白上调率为（63�6±2�2）％、（57�3±2�4）％，p21蛋白上调率为（54�6±3�4）％、（51�7±3�1）％。结论抑制Skp2基因表达可明显抑制移植瘤生长，Skp2基因有望成为肺癌基因治疗的新靶点。
展开▼
