期刊
CELLULAR SIGNALLING
卷 25, 期 12, 页码 2625-2633出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2013.08.028
关键词
Silibinin; Bladder cancer; Metastasis; EMT; CSC
类别
资金
- National Natural Science Foundation of China [NSFC 81202014, NSFC 81101936, NSFC 81072105, NSFC 81171953]
Muscle-invasive bladder cancer is associated with a high frequency of metastasis, and fewer therapies substantially prolong survival. Silibinin, a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including bladder cancer. Our and other previous studies have demonstrated that silibinin induced apoptosis and inhibited proliferation of bladder cancer cells, whether silibinin could suppress bladder cancer metastasis has not been elucidated. In the present study, we utilized a novel highly metastatic T24-L cell model, and found that silibinin treatment not only resulted in the suppression of cell migration and invasion in vitro, but also decreased bladder cancer lung metastasis and prolonged animal survival in vivo. Mechanistically, silibinin could inhibit glycogen synthase kinase-3 beta (CSK3 beta) phosphorylation, beta-catenin nuclear translocation and transactivation, and ZEB1 gene transcription that subsequently regulated the expression of cytokeratins, vimentin and matrix metalloproteinase-2 (MMP2) to reverse epithelial-mesenchymal transition (EMT). On the other hand, silibinin inhibited ZEB1 expression and then suppressed the properties of cancer stem cells (CSCs), which were evidenced as decreased spheroid colony formation, side population, and the expression of stem cell factor CD44. Overall, this study reveals a novel mechanism for silibinin targeting bladder cancer metastasis, in which inactivation of beta-catenin/ZEB1 signaling by silibinin leads to dual-block of EMT and stemness. (C) 2013 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据