藤黄酸通过核因子κB抑制剂激酶α/p65信号通路抑制人胃癌细胞系SGC-7901的侵袭  

Gambogic acid suppresses invasion in human gastric carcinoma SGC-7901 cells by modulating inhibitor of nuclear factor kappa-B kinase α/p65 signaling pathway in vitro

作　　者：仝雷 王世广 杨占峰[3] 岳丽晓 张玲玲 王鹏 TONG Lei;WANG Shi-guang;YANG Zhan-feng;YUE Li-xiao;ZHANG Ling-ling;WANG Peng(Department of Medical Morphology,Zhengzhou University of Industrial Technology,He'nan Xinzheng 451150,China;Department of Medical Function,Zhengzhou University of Industrial Technology,He'nan Xinzheng 451150,China;Department of Phylaxiology,Zhengzhou University of Industrial Technology,He'nan Xinzheng 451150,China)

机构地区：[1]郑州工业应用技术学院医学形态学教研室,河南新郑451150 [2]郑州工业应用技术学院医学机能学教研室,河南新郑451150 [3]郑州工业应用技术学院预防医学教研室,河南新郑451150

出　　处：《解剖学报》2020年第1期46-50,共5页Acta Anatomica Sinica

基　　金：河南省高等学校重点科研项目(19A310028);河南省卫生与计划生育委员会医学教育研究课题(wjlx2018238)。

摘　　要：目的探讨藤黄酸(GA)对人胃癌SGC-7901细胞侵袭能力的影响及其机制。方法用不同浓度藤黄酸、核因子κB抑制剂激酶(IKK16)和阳性对照药物5-氟尿嘧啶作用人正常胃黏膜上皮GES-1细胞和人胃癌SGC-7901细胞48 h后,采用细胞计数试剂盒8(CCK-8)检测细胞活力,Transwell侵袭实验检测SGC-7901细胞的侵袭能力,免疫印迹法检测波形蛋白(vimentin)、基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)的蛋白表达水平以及IKKα和p65的蛋白磷酸化水平。结果藤黄酸可剂量依赖性地抑制SGC-7901细胞活力,半数抑制浓度(IC50)分别为1. 89μmol/L,但对GES-1细胞活力无显著影响;5-氟尿嘧啶对GES-1和SGC-7901细胞均有抑制作用,IC50分别为7. 36μmol/L和199. 57μmol/L。低剂量藤黄酸或IKK16可抑制SGC-7901细胞侵袭,下调MMP-2、MMP-9和vimentin的蛋白表达水平以及抑制IKKα和p65蛋白磷酸化,并且两者联合作用时抑制作用更强。结论低剂量藤黄酸可在体外抑制人胃癌SGC-7901细胞侵袭,其机制可能与抑制IKKα/p65信号通路,继而下调MMP-2、MMP-9和vimentin蛋白表达水平相关。Objective To investigate the effect of gambogic acid( GA) on invasion in human gastric carcinoma SGC-7901 cells and its possible mechanism. Methods Cell counting kit-8( CCK-8) assay was performed to detect the effects of GA,inhibitor of nuclear factor kappa-B kinase( IKK) 16 and 5-fluorouracil( 5-FU) on cell activity of GES-1 and SGC-7901 cells. Cell invasion was assessed with Transwell invasion assay. Western blotting was used to analyze the protein levels of vimentin,matrix metalloproteinase 2( MMP-2) and MMP-9 and protein phosphorylation of IKKα and p65.Results The cell activity was significantly decreased in SGC-7901 cells treated with GA in a dose-dependent manner with a half inhibiton concentration( IC50) value of 1. 89 μmol/L. But GA had no significant influence on cell viability of GES-1 cells. Meanwhile,5-FU reduced the cell activity of GES-1 and SGC-7901 cells with IC50 values of 7. 36 μmol/L and199. 57 μmol/L respectively. Low-dose GA and IKK16 impaired separately the ability of invasion in SGC-7901 cells,and down-regulated the protein levels of MMP-2,MMP-9 and vimentin,and inhibited phosphorylation of IKKα and p65,while a stronger inhibition was showed when the combination of GA and IKK16 was used. Conclusion Low-dose GA might inhibit invasion of SGC-7901 cells via IKKα/p65 signaling pathway.

关 键 词：藤黄酸 胃癌 侵袭 SGC-7901细胞 核因子κB抑制激酶α 免疫印迹法 人 

分 类 号：R735.2[医药卫生—肿瘤]