基础医学与临床 ›› 2017, Vol. 37 ›› Issue (5): 643-647.

• 研究论文 • 上一篇    下一篇

纺锤菌素抑制胃癌细胞的侵袭和转移

查郎,彭旭东,王子卫   

  1. 重庆医科大学附属第一医院
  • 收稿日期:2016-12-12 修回日期:2017-01-17 出版日期:2017-05-05 发布日期:2017-04-19
  • 通讯作者: 王子卫 E-mail:wangziwei571@126.com
  • 基金资助:
    从胃癌中HMGA2下游调控靶点探讨上皮细胞间质转化和肿瘤细胞干性获取之间关系

Netropsin inhibits invasion and migration ability of gastric cancer cells

  • Received:2016-12-12 Revised:2017-01-17 Online:2017-05-05 Published:2017-04-19

摘要: 目的 探讨纺锤菌素(netropsin)对胃癌细胞侵袭转移能力的影响及其分子机制。方法 用Transwell检测胃癌细胞侵袭转移能力,用Westernblot检测EMT相关标志物E-cadherin和vimentin表达,用免疫荧光检测β-catenin的细胞定位,验证netropsin作用前后Wnt/β-catenin信号通路活性。结果 Netropsin浓度25μmol/L时对MKN28细胞增殖即有抑制作用,netropsin可以降低上皮标志物E-cadherin的表达,上调间质标志物vimentin的表达;netropsin可以通过抑制胃癌细胞的EMT降低胃癌细胞侵袭转移能力(P<0.05),同时可阻止β-catenin进入细胞核。结论 Netropsin可以通过与HMGA2竞争结合转录因子结合位点抑制Wnt/β-catenin信号通路,降低胃癌细胞EMT的发生,从而抑制胃癌细胞侵袭能力。

关键词: 胃肿瘤, 上皮间质转化, 纺锤菌素

Abstract: Objective To investigate theeffect of netropsin on migration and invasion ability of gastric cancer cells and its mechanisms. Methods To determine if netropsin inhibits migration and invasion of gastric cancer cells, Transwell migration and invasion assay was performed. Then Western blot was performed to detect expression of E-cadherin and vimentin in gastric cancer cells with or without presence in medium netropsin. Finally,immunofluorescence was performed to detect changes in the cellular localization of β-catenin to validate whether Wnt/β-catenin pathway was suppressed or not.Results Netropsinwith the concentration of 25 μmol/L had minimal inhibition effect on cell proliferation and was able to suppress ability of migration and invasion by inhibitingEMT in gastric cancer cells(P<0.05).Meanwhile netropsin was able to down-regulated the expression of epithelial markers E-cadherin and up-regulated the expression of mesenchymal marker vimentin. Finally, immunofluorescence showed that netropsin was able to block translocation of β-catenin from cytoplasm to nuclear.Conclusions Netropsin can inhibit EMT thereby suppressing migration and invasion of gastric cancer cells.The mechanism is that netropsin can compete with HMGA2 for transcription factor binding site thereby suppressing the Wnt/β-catenin pathway.

Key words: gastric carcinoma, epithelial-mesenchymal transitions(EMT), netropsin

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