Han Dan, Wu Gang, Chang Chan, Zhu Fang, Xiao Yin, Li Qiuhui, Zhang Tao, Zhang Liling
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Oncotarget. 2015 Dec 1;6(38):40907-19. doi: 10.18632/oncotarget.5723.
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.
双硫仑（DSF）是一种戒酒药物，据报道它是核因子κB（NF-κB）的抑制剂。NF-κB参与上皮-间质转化（EMT）以及乳腺癌干细胞（CSCs）的自我更新。在本研究中，我们用转化生长因子-β（TGF-β）处理MCF-7和MDA-MB-231乳腺癌细胞以诱导EMT和癌症干细胞样特征，并研究DSF是否能逆转这一过程。我们发现DSF以剂量依赖性方式抑制TGF-β诱导的乳腺癌细胞EMT。此外，DSF抑制与EMT相关的干细胞样特征、肿瘤细胞的迁移和侵袭以及异种移植模型中的肿瘤生长。NF-κB的激活与EMT和干细胞样细胞有关。我们得出结论，DSF可抑制NF-κB活性并下调ERK/NF-κB/蜗牛（Snail）通路，从而逆转EMT和干细胞样特征。我们的数据表明，DSF通过抑制ERK/NF-κB/Snail通路来抑制乳腺癌细胞中的EMT和干细胞样特性。
