姜黄素下调HIF-1α/MMP-9通路抑制人胃癌裸鼠移植瘤生长  

Curcumin Inhibits Human Gastric Cancer Growth in Xenograft Murine Model through Downregulation of HIF-1α/MMP-9 Pathway

作　　者：何丽琳[1] 沈永祥[2] 周中银[3] 徐禹[4] 刘梓良[1] 

机构地区：[1]天门市第一人民医院肿瘤科,湖北天门431700 [2]天门市第一人民医院消化科,湖北天门431700 [3]武汉大学人民医院消化内科 [4]武汉大学中南医院肿瘤科

出　　处：《肿瘤防治研究》2013年第8期737-742,共6页Cancer Research on Prevention and Treatment

基　　金：国家自然科学基金青年基金资助项目(81000537)

摘　　要：目的研究姜黄素对人胃癌细胞株BGC-823裸鼠皮下移植瘤的生长抑制作用及其机制。方法以0、1、5、10、20、50mg/L的姜黄素处理BGC-823细胞24或48h,甲基噻唑盐(MTT)法及Transwell分析细胞增殖和侵袭能力;荷瘤裸鼠检测姜黄素对肿瘤生长影响,同时Western blot检测瘤体内HIF-1α、MMP-9蛋白的表达;荧光素酶报告基因系统检测姜黄素对HIF-1α及HIF-1α对MMP-9启动子区域调控。结果姜黄素处理人胃癌细胞BGC-823后,在体内体外的生长均受到抑制且作用呈量效依赖关系;细胞侵袭能力明显降低;HIF-1α、MMP-9蛋白的表达降低。姜黄素通过转录水平抑制HIF-1α及MMP-9的启动子活性。结论姜黄素在体内外均抑制胃癌的生长,它可以通过降低HIF-1α活性,下调MMP-9水平,从而抑制肿瘤侵袭,发挥抗肿瘤作用。Objective To study the mechanism of curcumin inhibition of transplanted tumor growth in gastric cancer xenograft nude mice.Methods BGC-823 cells were treated with curcumin at concentration of 0,1,5,10,20,50 mg/L for 24 h or 48 h,cells proliferation ability was detected by the 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT） and cells invasion ability was detected by transwell assay.Gastric cancer xenograft nude mice model was established to assess the effect of curcumin inhibition on the xenografts.Additionally,Western blot was used to assess HIF-1α and MMP-9 protein expression levels in the xenografts.Luciferase assay was used to assessed the MMP-9 regulation by HIF-1α,and HIF-1α regulation by curcumin.Results Curcumin inhibited the proliferation of BGC-823 cells,and the effects were dose dependent in vivo and in vitro.The cells invasion ability was significantly reduced.HIF-1α and MMP-9 proteins expression were decreased.Curcumin inhibited HIF-1αand MMP-9 promoter activities on transcriptional level.Conclusion Curcumin inhibited human gastric cancer growth in vivo and in vitro through targeting HIF-1α/MMP-9 pathway transcription suppression,thereby inhibiting tumor invasion,as an anti-tumor effect.

关 键 词：姜黄素 人胃癌移植瘤 HIF-1Α 

分 类 号：R735.2[医药卫生—肿瘤]