Objective This study was to investigate the effect of PARG-shRNA on liver metastasis of colorectal carcinoma CT26 cell line in mice. Methods Mice were divided into three groups. Animal model for liver metastases of colorectal cancer was established by intrasplenic inoculation of colorectal carcinoma cell in BALB/c mice. CT26 cells transfected with empty vector and CT26 cells transfected with PARG-shRNA were inoculated into spleen caspsule. CT26 cells transfected with empty vector and untransfected CT26 cells served as control. The change of spleen and liver metastases carcinoma nodules were observed and counted. The expressions of PARG, PARP, NF-kB, integrin-β1, MMP-2, MMP-9 in spleen transplant tumor were measured by Western blot analysis. Results The size of spleen transplant tumor and liver metastatic nodules in transfected group were smaller than that in the control groups ( P < 0. 05). The expression of PARG (0. 0105±0.0028), PARP (0.1786 ± 0.024), NF-κB (0. 1678 ± 0.0359), integrin-β1, MMP-2 and MMP-9 in transfected group was weaker than that in the control groups ( P < 0. 05). Conclusions The growth of spleen transplant tumor and liver metastases can be inhibited by PARG gene silencing in CT26 cells probably through down-regulation of PARP, NF-κB and NF-κB-dependent downstream gene.%目的 探讨多聚(腺苷二磷酸核糖)水解酶(PARG)基因沉默对小鼠结肠癌CT26细胞肝脏转移的影响.方法 小鼠随机分成3组,脾脏包膜下注射PARG-shRNA慢病毒载体转染CT26细胞悬液,以未转染组和空载体转染组为对照.比较各组脾脏肝脏瘤结节数量、大小;Western blot检测PARG、PARP、NF-κB、integrin-β1、MMP-2和MMP-9的表达.结果 PARG基因沉默组小鼠脾脏移植瘤大小及肝脏转移瘤结节分级均明显低于对照组(P＜0.05);PARG基因沉默后,脾脏移植瘤组织中PARG(0.0105±0.0028)、PARP(0.1786±0.024)、NF-κB(0.1678±0.0359)、integrin-p1、MMP-2和MMP-9的蛋白表达量明显低于对照组(P＜0.05).结论 PARG基因沉默后能抑制小鼠脾脏移植瘤的生长及肝脏转移瘤结节的形成,其作用可能是通过下调PARP、NF-κB及其下游依赖性基因的表达而实现的.
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