Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway.
Disulfiram inhibits TGF-β-induced epithelial-mesenchymal transition and stem-like features in breast cancer via ERK/NF-κB/Snail pathway.
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双硫仑通过 ERK/NF-κB/Snail 途径抑制乳腺癌中 TGF-β 诱导的上皮间质转化和干细胞样特征
DOI：
10.18632/oncotarget.5723
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发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Han D;Wu G;Chang C;Zhu F;Xiao Y;Li Q;Zhang T;Zhang L
双硫兰是一种抗酒精中毒药物，已被报道为核因子-κB的抑制剂。核因子-κB参与了乳腺癌干细胞上皮-间充质转化和自我更新。在本研究中，我们用转化生长因子-β处理乳腺癌细胞MCF7和MDAMB-231，诱导其分化为内胚层和肿瘤干细胞样特征，并研究其是否能逆转这一过程。我们发现丹参酮以剂量依赖的方式抑制转化生长因子-β诱导的乳腺癌细胞内皮细胞转化。此外，在异种移植模型中，DSF还抑制了EMT相关的干细胞样特征、肿瘤细胞的迁移和侵袭以及肿瘤的生长。NF-κB的激活与内胚层转化和干细胞样细胞有关。结论：丹参口服液可抑制NF-κB活性，下调ERK/NF-κB/Snail通路，逆转EMT和干细胞样特征。我们的数据表明，DSF抑制乳腺癌细胞的EMT和干细胞样特性，这与抑制ERK/NF-κB/Snail途径有关。
Disulfiram (DSF), an anti-alcoholism drug, has been reported as an inhibitor of NF-κB. NF-κB is involved in epithelial-mesenchymal transition (EMT) and self-renewal of breast cancer stem cells (CSCs). In this study, we treated MCF-7 and MDA-MB-231 breast cancer cells with TGF-β to induce EMT and cancer stem-like features and studied whether DSF can reverse this process. We found that DSF inhibited TGF-β induced EMT in breast cancer cells in a dose-dependent manner. Also, DSF inhibited EMT-associated stem-like features, migration and invasion of tumor cells as well as tumor growth in xenograft model. The activation of NF-κB was linked with EMT and stem-like cells. We conclude that DSF can suppress NF-κB activity and downregulate ERK/NF-κB/Snail pathway, leading to reverse EMT and stem-like features. Our data suggest that DSF inhibits EMT and stem-like properties in breast cancer cells associated with inhibition of the ERK/NF-κB/Snail pathway.