Resveratrol Sensitizes Tamoxifen in Antiestrogen-Resistant Breast Cancer Cells with Epithelial-Mesenchymal Transition Features

International Journal of Molecular Sciences

Xiao-Peng Shi²  Shan Miao⁵  Yin Wu²  Wei Zhang⁴  Xiao-Fang Zhang²  Hua-Zhao Ma¹  Hai-Li Xin³  Juan Feng²  Ai-Dong Wen² 

[1] Outpatient Department, Institute of Armored Force, Bengbu 233050, China; E-Mail:;Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China; E-Mails:;Surgery Pharmacy of Department of Pharceutical Care, General Hospital of PLA, Beijing 100853, China; E-Mail:;School of Public Health, Fourth Military Medical University, Xi’an 710032, China; E-Mail:;Institute of Materia Medica, Fourth Military Medical University, Xi’an 710032, China; E-Mail:

关键词: breast cancer;    tamoxifen;    resistance;    epithelial-mesenchymal transition;    resveratrol;   

DOI  :  10.3390/ijms140815655

来源: mdpi

【 摘 要 】

Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7/TR breast cancer cells and showed that MCF-7/TR cells underwent EMT driven by enhanced endogenous TGF-β/Smad signaling. Ectopic supplement of TGF-β promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7/TR cells. Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-β production and Smad phosphorylation. In particular, 50 μM resveratrol had minor effects on MCF-7/TR cell proliferation, but could significantly attenuate endogenous TGF-β production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-β/Smad-dependent.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland