中文摘要：

目的 探索APE1敲低后骨肉瘤细胞恶性表型受抑的可能机制，以及APE1相互作用的可能分子。方法 应用免疫印迹和AP核酸内切酶活性检测确证合成APE1 siRNA对人体骨肉瘤细胞HOSAPE1基因的敲低作用；应用GEAr-ray“Q系列eDNA微阵列研究HOS细胞APE1敲低后基因表达谱的改变。结果 APE1 siRNA对HOS细胞APE1基因具有特异性“敲低”作用，其抑制效率为91．5％。APE1抑制对eDNA微阵列六族途径均有影响，其中对细胞周期族基因影响较少；96个基因中有42个基因有明显变化（43．8％），其中CDK4、FGFR2、KAI1和NCAM1表达上升，其余38个基因表达均呈下降。结论 APE1的敲低对骨肉瘤细胞的细胞周期及DNA损伤、细胞凋亡、信号转导、细胞黏附、血管生成、肿瘤转移途径基因均有影响。

英文摘要：

Objective To explore the molecular mechanism of inhibited malignant phenotype by knockdown of apurinic/apyrimidinic endonuclease （ APE1 ） in human osteosarcoma cell HOS, as well as the possible interacting molecules among APE1. Methods Knock-down of APE1 by synthesized APE1 siRNA in HOS cell was identified first by Western blotting and AP endonuclease assay, then the gene profile was determined with GEArrayTM series Human CancerPathwayFinder gene array. Results The specific knock-down of APE1 was found in HOS cell transfected with APE1 siRNA, and its inhibited rate was 91.5%. Six biological pathways of the gene array were involved in HOS cell after knock-down of APE1, but the cell cycle pathway was less influenced. Forty-two out of 96 genes were altered （43.8%） , in which only CDK4, FGFR2, KAI1 and NCAM were increased, 38 others were decreased. Conclusion The knock-down of APE1 was detected to be involved in all the pathways including cell cycle and DNA repair, apoptosis, signal transduction, adhesion, angiogenesis, invasion and metastasis. These findings are significant to further elucidate APE1 role in tumor genesis and to provide experimental evidence for gene therapy targeting APE1 gene in the future.