槲皮素通过调控p38/GSK3β途径调节上皮-间质转化抑制乳腺癌侵袭和转移
Quercetin Inhibits Invasion and Metastasis of Breast Cancer by Regulating Epithelial-mesenchymal Transition via the p38/GSK3β Pathway
李之令 1陈杰 2陈庆 1颜红 1王飞 1陈琼1
作者信息
- 1. 四川省凉山州第二人民医院甲乳外科,西昌 615000
- 2. 四川省人民医院乳腺外科,成都 610041
- 折叠
摘要
目的:探讨黄酮类化合物槲皮素对三阴性乳腺癌(TNBC)细胞MCF-7侵袭和转移的抑制作用及其具体作用机制.方法:采用0、25、50、100μM槲皮素处理乳腺癌细胞株MCF-7,命名为对照组、25μM组、50μM组和100μM组.分别通过Transwell检测细胞的侵袭和转移,Western Blotting检测上皮间质转化(EMT)相关标记物的表达水平以及p38/GSK3β途径分子的蛋白磷酸化水平.应用小分子抑制剂干扰相关通路后检测细胞侵袭和转移的变化.结果:槲皮素可以浓度依赖的方式抑制MCF-7的迁移、侵袭,E-cadherin的表达上升,N-cadherin和Vi-mentin表达下降.槲皮素能够以浓度依赖的方式降低p38和GSK3β途径分子的蛋白磷酸化水平.采用p38和GSK3β的抑制剂使E-cadherin的表达上升,N-cadherin和Vimentin表达下降,并抑制MCF-7的迁移和侵袭.结论:槲皮素可抑制TNBC侵袭和转移,其机制主要是通过抑制p38/GSK3β途径实现从EMT向MET的转变.
Abstract
Objective:To explore whether the flavonoid quercetin effectively regulates EMT-related molecular signals in MCF-7 in triple negative breast cancer(TNBC)cells.Method:Breast cancer cell line MCF-7 was treated with 0,25,50,100μM quercetin and named control group,25μM group,50μM group,and 100μM group.The in-vasion and metastasis of cells were detected by Trans well,and the expression levels of EMT-related markers and protein phosphorylation levels of p38/GSK3β pathway molecules were detected by Western-blotting.Changes in cell invasion and metastasis were detected after small molecule inhibitors were applied to interfere with relevant path-ways.Results:Quercetin inhibited the migration and invasion of MCF-7 in a concentration dependent manner.The expression of E-cadherin was increased,while the expression of N-cadherin and Vimentin was decreased.Quercetin reduced protein phosphorylation levels of p38 and GSK3β pathway molecules in a concentration-dependent manner.The use of p38 and GSK3β inhibitors increased the expression of E-cadherin,decreased the expression of N-cadherin and Vimentin,and inhibited the migration and invasion of MCF-7.Conclusion:Quercetin can inhibit TNBC invasion and metastasis,mainly through inhibiting p38/GSK3β pathway to achieve the transition from EMT to MET.
关键词
槲皮素/p38/GSK3β/上皮-间质转化/乳腺癌Key words
Quercetin/Epithelial-mesenchymal/p38/GSK3β pathway/Breast cancer引用本文复制引用
基金项目
四川省重点研发项目(2023YFS0132)
四川省凉山州科技计划重点研发项目(21ZDYF0039)
出版年
2024
NETL
NSTL
万方数据