S100A4协同HIF-1通过WNT/β-catenin通路调控胃癌细胞SGC-7901的迁移和侵袭  

S100A4 cooperates with HIF-1 to regulate migration and invasion of gastric cancer cells via WNT/β-catenin pathway

作　　者：廖煜 任宁川 房殿亮 胡永强 黄剑[1] 曾波[1] 何平[1] 杨天文[1] 

机构地区：[1]重庆医科大学附属永川医院消化内科,重庆402160

出　　处：《中国肿瘤生物治疗杂志》2017年第9期955-959,共5页Chinese Journal of Cancer Biotherapy

基　　金：重庆市永川区科委项目(No.Ycstc;2013nc8017)~~

摘　　要：目的:探讨S100A4在低氧条件下对胃癌细胞SGC-7901迁移及侵袭的作用及其可能的机制。方法:将化学合成的si-S100A4质粒和阴性对照(si-Ctrl)质粒分别转染胃癌细胞株SGC-7901,根据培养条件的不同分为常氧条件(normal,Nor)+si-S100A4组、Nor+si-Ctrl组、低氧条件(hypoxia,Hyp)+si-Ctrl)组、Hyp+si-S100A4组。应用Western blotting检测低氧条件下胃癌SGC-7901细胞中HIF-1及S100A4蛋白的表达变化,检测低氧条件下胃癌细胞中抑制S100A4的表达对细胞中S100A4、β-catenin及TCF-4表达的影响,Transwell小室法分别检测低氧及S100A4对胃癌SGC-7901细胞迁移及侵袭能力的影响。结果:低氧条件下:(1)胃癌SGC-7901细胞中HIF-1和S100A4表达水平均明显升高(3.12±0.23 vs 1.02±0.05,P<0.01;2.75±0.32 vs 1.05±0.07,P<0.01),且两者变化明显相关(r=0.67,P<0.01);(2)胃癌SGC-7901细胞的侵袭及迁移能力增加[(223.31±35.12)vs(131.29±26.40)、(142.27±26.37)个,P<0.05]。干扰低氧条件中S100A4的表达:(1)明显减少低氧对细胞中β-catenin及TCF-4的促进作用(均P<0.01);(2)明显减少低氧对SGC-7901细胞的侵袭及迁移能力的促进作用[(161.37±31.02)vs(88.21±22.42)、(95.36±21.29)个,P<0.05]。结论:S100A4能够促进胃癌细胞SGC-7901的迁移和侵袭,该作用可能是通过S100A4协同HIF-1通过Wnt/β-catenin通路的调控实现的。Objective：To explore the effects of S100A4 on the migration and invasion capacity of gastric cancer SGC-7901 cells under hypoxia condition,and to identify the possible mechanism;Methods：The gastric cancer cell line,SGC-7901 was transfected with chemically synthesized si-S100A4 plasmidand si-control plasmid（negative control）.Depending on the different culture conditions,SGC-7901 cells were further divided into four groups：normoxia（Nor）＋si-S100A4 group,Nor＋si-Ctrl group,hypoxia（Hyp） ＋ si-Ctrl group and Hyp＋si-S100A4 group.Under the hypoxia condition,the protein expressions of HIF-1 and S100A4 in SGC-7901 cells were detected using the Western blotting assay.The effects of siS100A4 on the expression of S100A4,β-catenin and TCF-4 upon hypoxia condition were further explored.Moreover,the Transwell assay were conducted to explore the effects of hypoxia and si-S100A4 on the migration and invasion capacity of gastric cancer SGC-7901 cells.Results：Under the hypoxia condition,（1） the expression of HIF-1 and S100A4 in gastric cancer SGC-7901 cells were significantly up-regulated（3.12±0.23 vs 1.02±0.05,P〈0.01;2.75±0.32 vs 1.05±0.07,P〈0.01）,and the expressions were significantly correlated（r=0.67,P〈0.01）;（2） the migration and invasion capacity of SGC-7901 cells were significantly increased（223.31 ± 35.12 vs 131.29 ± 26.40,142.27 ± 26.37,P〈0.05].Under hypoxia ＋ siS100A4 condition：（1） the promotion effect of hypoxia on the expressions of β-catenin and TCF-4 was significantly reduced（all P〈0.01）;（2） the promotion effect of hypoxia on the migration and invasion ability of SGC-7901 cells was significantly decreased（161.37±31.02 vs 88.21±22.42、95.36±21.29,P〈0.05）.Conclusion：S100A4 promoted the migration and invasion capacity of gastric cancer SGC-7901 cells,which was possibly achieved by synergistically working with HIF-1 to regulate Wnt/β-catenin pathway.

关 键 词：缺氧诱导因子-1 S100A4蛋白 WNT/Β-CATENIN通路 胃癌 侵袭 

分 类 号：R735.2[医药卫生—肿瘤] R730.2[医药卫生—临床医学]