中文摘要：

目的探讨聚腺苷二磷酸核糖水解酶[poly-（ADP-ribose）glycohydrolase,PARG]基因沉默经AKT途径对大肠癌细胞肝转移的影响及其可能机制。方法用未转染的CT26细胞、慢病毒空载体转染的CT26细胞和PARG-shRNA慢病毒载体转染的CT26细胞接种至BALB/c小鼠脾包膜下,建立相应的肝转移模型,比较各组脾脏移植瘤及肝脏转移瘤结节的差异。进一步用Western blot法检测各组脾脏移植瘤PARG、聚腺苷酸二磷酸核糖转移酶-1[poly-（ADP-ribose）polymerase-1,PARP-1]、蛋白激酶B（protein kinase B,PKB,即AKT）、P-AKT473、核转录因子-κB p65（nuclear factor-kappaB p65,NF-κB p65）、血管内皮细胞生长因子（vascularendothelial growth factor,VEGF）及碱性成纤维细胞生长因子（basic fibroblast growth factor,bFGF,即FGF-2）的表达。结果与对照组相比,PARG沉默组脾脏移植瘤体积较小（P〈0.05）,肝转移瘤结节数量减少（P〈0.05）;脾脏移植瘤的PARG、PARP-1、NF-κB p65、VEGF、FGF-2蛋白表达显著减弱（P均〈0.05）,P-AKT473的表达明显增强（P〈0.05）。结论 CT26细胞系的PARG表达抑制后,可以抑制大肠癌CT26细胞移植瘤的生长与转移,这可能与PARG抑制使AKT磷酸化增强,从而降低了VEGF、FGF-2等血管生成相关因子的表达有关。

英文摘要：

Objective To investigate the effect of silencing poly-（ADP-ribose）glycohydrolase（PARG） on murine CT26 colon cancer cell xenografted tumor models and its possible mechanisms.Methods Xenografted tumor models were established and grouped as intrasplenic injection of colonic carcinoma cells（CT26） being untransfected,transfected with empty vector and transfected with PARG-shRNA.All groups were compared with each other in order to ascertain differences of carcinoma in spleen and liver.Ultimately,the expressions of PARG,poly-（ADP-ribose） polymerase-1（PARP-1）,protein kinase B（PKB,i.e.AKT）,P-AKT473,nuclear factor-kappaB p65（NF-κB p65）,vascular endothelial growth factor（VEGF） and basic fibroblast growth factor（bFGF,i.e.FGF-2） of splenic xenografted tumors were detected by Western blot.Results Compared with the control group, there were statistically significant decrease of the expressions of PARG,PARP-1,NF-κB p65,VEGF,FGF-2 and volumes of intrasplenic xenografted tumors（P0.05） as well as the amounts of liver metastases（P0.05）,but there was statistically significant increase of the expression of P-AKT473 of the intrasplenic xenografted tumors（P0.05） in PARG-silenced group.Conclusions The knock-down of PARG can inhibit growth and metastasis of CT26 colon cancer cells xenografted tumor,which may be attributed to the reduction in the expressions of VEGF and FGF-2 by enhancing AKT phosphorylation.