Journal
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume 38, Issue -, Pages -Publisher
BMC
DOI: 10.1186/s13046-019-1196-x
Keywords
CoQ(0); TNBC; EMT; Metastasis; Human epidermal growth factor receptor 2; TGF-1; ROS
Categories
Funding
- Ministry of Science and Technology, Taiwan [MOST-106-2320-B-039-054-MY3, MOST-107-2320-B-039-013-MY3, CMU 107-S-47]
- Chinese Medicine Research Center, China Medical University from the Featured Areas Research Center Program [CMRC-CHM-8]
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BackgroundBreast cancer is the most prevalent cancer among women. In triple-negative breast cancer (TNBC) cells, a novel quinone derivative, coenzyme Q(0) (CoQ(0)), promotes apoptosis and cell-cycle arrest. This study explored the anti-epithelial-mesenchymal transition (EMT) and antimetastatic attributes of CoQ(0) in TNBC (MDA-MB-231).MethodsInvasion, as well as MTT assays were conducted. Lipofectamine RNAiMAX was used to transfect cells with -catenin siRNA. Through Western blotting and RT-PCR, the major signaling pathways' protein expressions were examined, and the biopsied tumor tissues underwent immunohistochemical and hematoxylin and eosin staining as well as Western blotting.ResultsCoQ(0) (0.5-2M) hindered tumor migration, invasion, and progression. Additionally, it caused MMP-2/-9, uPA, uPAR, and VEGF downregulation. Furthermore, in highly metastatic MDA-MB-231 cells, TIMP-1/2 expression was subsequently upregulated and MMP-9 expression was downregulated. In addition, CoQ(0) inhibited metastasis and EMT in TGF-/TNF--stimulated non-tumorigenic MCF-10A cells. Bioluminescence imaging of MDA-MB-231 luciferase-injected live mice demonstrated that CoQ(0) significantly inhibited metastasis of the breast cancer to the lungs and inhibited the development of tumors in MDA-MB-231 xenografted nude mice. Silencing of -catenin with siRNA stimulated CoQ(0)-inhibited EMT. Western blotting as well as histological analysis established that CoQ0 reduced xenografted tumor development because apoptosis induction, cell-cycle inhibition, E-cadherin upregulation, -catenin downregulation, and metastasis and EMT regulatory protein modulation were observed.ConclusionsCoQ(0) inhibited the progression of metastasis as well as EMT (in vitro and in vivo). The described approach has potential in treating human breast cancer metastasis.
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