摘要
目的探讨地高辛与他莫昔芬联合用药对MCF-7细胞增殖、迁移和侵袭的影响及可能的机制。方法MTT法、平板克隆和流式细胞术实验检测他莫昔芬和地高辛联合用药对MCF-7细胞增殖和凋亡的影响,划痕和Transwell实验检测他莫昔芬与地高辛联合用药对MCF-7细胞迁移和侵袭的影响,Western blot检测他莫昔芬和地高辛联合用药对MCF-7细胞中相关蛋白表达的影响。结果MTT、平板克隆和流式细胞术结果显示,地高辛可与他莫昔芬可协同抑制MCF-7细胞增殖并促进其凋亡;划痕愈合实验和Transwell实验结果显示地高辛与他莫昔芬联合用药可协同抑制MCF-7细胞的迁移和侵袭;Western blot结果显示地高辛与他莫昔芬联合用药可协同抑制PI3K、p-PI3K、p-AKT、Bcl-2、N-cadherin、Vimentin的表达,促进Bax、cleaved-caspase-3、cleaved-caspase-9、E-cadherin的表达。结论他莫昔芬联合地高辛用药可协同抑制乳腺癌MCF-7细胞的增殖、迁移和侵袭,促进凋亡,其机制可能与其抑制PI3K-AKT信号通路及EMT有关。
Aim To investigate the effect of digoxin combined with tamoxifen on proliferation,migration,invasion of breast cancer MCF-7 cells and the possible underlying mechanism.Methods MTT,colony formation and flow cytometry were used to detect the effect of the combination therapy of tamoxifen and digoxin on proliferation and apoptosis in MCF-7 cells.Wound healing assay and transwell assay were used to detect the effect of the combination therapy of tamoxifen and digoxin on migration and invasion of MCF-7 cells.Western blot was used to detect the effect of the combination therapy of tamoxifen and digoxin on the expression of related proteins in MCF-7 cells.Results MTT,colony formation assay and flow cytometry results showed that digoxin and tamoxifen synergistically inhibited the proliferation and promoted the apoptosis of MCF-7 cells.Wound healing and transwell assay results showed that digoxin and tamoxifen synergistically inhibited the migration and invasion of MCF-7 cells.Western blot results showed that digoxin and tamoxifen synergistically inhibited the expression of PI3K,p-PI3K,p-AKT,Bcl-2,N-cadherin,Vimentin and promoted the expression of Bax,cleaved-caspase-3,cleaved-caspase-9,E-cadherin of MCF-7 cells.Conclusions Digoxin combined with tamoxifen can synergistically inhibit the proliferation,migration,invasion and induce apoptosis of MCF-7 cells,the possible mechanism of which may involve the suppression of PI3K-Akt signaling pathway and epithelial-mesenchymal transition(EMT).
作者
沈敬堃
朱海涛
梅珈彬
潘际刚
王璐
王旭东
SHEN Jing-kun;ZHU Hai-tao;MEI Jia-bin;PAN Ji-gang;WANG Lu;WANG Xu-dong(Dept of Physiology,School of Basic Medicine,Guizhou Medical University,Guiyang 550025,China;Dept of Hepatobiliary Surgery,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,China)
出处
《中国药理学通报》
CSCD
北大核心
2021年第9期1256-1263,共8页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 31660345)。
关键词
地高辛
他莫昔芬
乳腺癌细胞
协同作用
增殖
上皮-间质转换
digoxin
tamoxifen
breast cancer cells
synergistic action
proliferation
epithelial-mesenchymal transition
