摘要
研究黄芩素对人食管鳞癌转移的影响及可能的作用机制。采用划痕实验、Transwell迁移和侵袭实验分别考察黄芩素对食管鳞癌细胞(EC9706和KYSE30)迁移和侵袭能力的影响;使用KYSE30细胞构建裸鼠肺转移模型考察黄芩素在体内对食管鳞癌转移的影响。本文中动物福利和实验过程均遵循河南大学动物伦理委员会的规定。使用Western blot法检测黄芩素对食管鳞癌细胞中ERK/ELK-1/Snail信号通路相关蛋白表达的影响。实验结果显示:黄芩素能够显著地降低EC9706和KYSE30细胞的迁移和侵袭能力;黄芩素在体内对食管鳞癌转移也具有很强抑制作用;分子机制研究发现,黄芩素显著地降低ERK1/2(extracellular signal-regulated kinase 1/2,T202/Y204)和ELK-1(ETS-domain containing protein-1,S383)的磷酸化,下调果蝇蜗牛同源蛋白(Snail)、神经型钙黏蛋白(N-cadherin)和波形蛋白(Vimentin)的表达,同时促进上皮型钙黏蛋白(E-cadherin)表达;使用ERK1/2抑制剂U0126或siRNA能够显著地增强黄芩素对以上蛋白的调节作用。综上所述,黄芩素可能通过调节ERK/ELK-1/Snail信号通路抑制食管鳞癌细胞迁移、侵袭和转移。
This study aims to investigate the effect of baicalein on the metastasis of esophageal squamous cell carcinoma(ESCC)cells,and to elucidate the potential molecular mechanisms.Wound healing and Transwell migra‐tion and invasion assays were performed to detect the effect of baicalein on the migration and invasion of EC9706 and KYSE30 cells;the nude mice models of lung metastasis were applied to examine the function of baicalein in metastasis of ESCC by using KYSE30 cells.All animals were received humane care according to the Institutional Animal Care Guidelines approved by the Experimental Animal Ethical Committee of Henan University.Western blot assay was used to detect the protein levels of ERK/ELK-1/Snail signaling pathway.The data showed that baicalein significantly inhibited the migration and invasion of EC9706 and KYSE30 cells;Mechanistically,baicalein treatment led to a dramatically reduced expression of phosphorylated extracellular signal-regulated kinase 1/2(p-ERK1/2,T202/Y204),p-ETS-domain containing protein-1(p-ELK-1,S383),Snail,N-cadherin,and Vimentin,and a statistical increase of E-cadherin expression in EC9706 and KYSE30 cells;Furthermore,the inhibition of ERK1/2 by U0126 or siRNA remarkably enhanced the effect of baicalein on the above proteins.In summary,baicalein probably inhibits the migration,invasion,and metastasis of ESCC cells via blocking the ERK/ELK-1/Snail signaling pathway.
作者
王建涛
曾荟珊
韦珍
陈亮
WANG Jian-tao;ZENG Hui-shan;WEI Zhen;CHEN Liang(Henan Medical Technician College,Kaifeng 475003,China;School of Pharmacy,Henan University,Kaifeng 475004,China;The Key Laboratory of Natural Medicine and Immuno-Engineering,Henan University,Kaifeng 475004,China)
出处
《药学学报》
CAS
CSCD
北大核心
2021年第1期224-230,共7页
Acta Pharmaceutica Sinica
基金
河南省高等学校重点科研项目(20A350002)
河南省重点研发与推广专项科技攻关资助项目(202102310156)。
关键词
黄芩素
食管鳞癌
迁移
侵袭
转移
果蝇蜗牛同源蛋白
baicalein
esophageal squamous cell carcinoma
migration
invasion
metastasis
Snail
