PARG抑制对小鼠结肠癌CT26细胞VEGF-C蛋白表达调控的初步研究  

Effect of PARG inhibition on VEGF-C expression in mice colon cancer CT26 cells

作　　者：吴伟强[1] 王娅兰[1] 颜佳欣[1] 潘娟[1] 

机构地区：[1]重庆医科大学基础医学院病理学教研室,分子医学与肿瘤研究中心,重庆400016

出　　处：《第三军医大学学报》2011年第14期1451-1454,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30870946)~~

摘　　要：目的初步探讨多聚(腺苷二磷酸核糖)水解酶[poly-(ADP-ribose)glycohydrolase,PARG]抑制对小鼠结肠癌CT26细胞VEGF-C蛋白表达影响。方法分为实验组(GLTN处理)与对照组(GLTN未处理),采用Western blot法检测2组小鼠结肠癌CT26细胞的PARG、PARP-1、NF-κB及VEGF-C的蛋白表达变化;RT-PCR分析实验组与对照组的VEGF-C mRNA水平变化;ELISA法检测2组小鼠结肠癌CT26细胞上清液VEGF-C蛋白表达变化。结果 PARG抑制后小鼠结肠癌CT26细胞表达的PARG和NF-κB蛋白较对照组下降(P<0.01),PARP-1和VEGF-C蛋白较对照组降低(P<0.01)。RT-PCR结果显示,实验组CT26细胞株VEGF-C mRNA表达[相对灰度值为(0.39±0.08)]较对照组[相对灰度值为(0.63±0.04)]显著下降(P<0.01)。实验组小鼠结肠癌CT26细胞分泌的VEGF-C蛋白量[(95.86±5.43)pg/ml]较对照组[(1 99.32±0.75)pg/ml]明显降低(P<0.05)。结论在小鼠结肠癌CT26细胞中,抑制PARG可下调PARP-1和NF-κB的表达,从而使VEGF-C表达下降,这可能在抑制肿瘤淋巴管形成中起重要作用。Objective To investigate the role of poly（ADP-ribose） glycohydrolase（PARG） inhibition in the regulation of vascular endothelial growth factor C（VEGF-C） expression in colon cancer cell CT26 in mice.Methods CT26 cells were divided into an experimental group and a control group.CT26 cells in the experimental group were treated with PARG inhibitor gallotannin（GLTN）.The expression levels of PARG,PARP-1,NF-κB and VEGF-C were detected by Western blotting.The VEGF-C mRNA level changes of the two groups were detected by RT-PCR.The VEGF-C protein level changes in the supernatants of cultured CT26 cells in the two groups were measured by enzyme-linked immunosorbent assay（ELISA）.Results Western blot results showed that the PARG,PARP-1,NF-κB,and VEGF-C protein levels in the experimental group were significantly lower than those in the control group（P0.01）.The VEGF-C mRNA level（0.39±0.08） and the VEGF-C protein level（95.86±5.43） pg/ml in the experimental group were significantly lower than that（0.63±0.04） in the control group（P0.01） and that（199.32±0.75） pg/ml in the control group（P0.05）.Conclusion In mouse colon cancer cell CT26,PARG inhibition dramatically reduces VEGF-C expression by down-regulating PARP-1 and NF-κB expression in the nuclear factor NF-κB signaling pathway.PARG inhibition may have an anti-lymphangiogenc effect and contribute to the prevention of metastatic dissemination via lymph system.

关 键 词：多聚(腺苷二磷酸核糖)水解酶 多聚(腺苷二磷酸核糖)聚合酶 NF-ΚB 血管内皮生长因子C 肿瘤淋巴管形成 

分 类 号：R735.35[医药卫生—肿瘤] R394.3[医药卫生—临床医学]