Oncotarget

Research Papers:

Aspirin regulation of c-myc and cyclinD1 proteins to overcome tamoxifen resistance in estrogen receptor-positive breast cancer cells

Ran Cheng, Ya-Jing Liu, Jun-Wei Cui, Man Yang, Xiao-Ling Liu, Peng Li, Zhan Wang, Li-Zhang Zhu, Si-Yi Lu, Li Zou, Xiao-Qin Wu, Yu-Xia Li, You Zhou, Zheng-Yu Fang and Wei Wei _

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Oncotarget. 2017; 8:30252-30264. https://doi.org/10.18632/oncotarget.16325

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Abstract

Ran Cheng1,*, Ya-Jing Liu2,*, Jun-Wei Cui1, Man Yang1, Xiao-Ling Liu1, Peng Li1, Zhan Wang1, Li-Zhang Zhu1, Si-Yi Lu1, Li Zou1, Xiao-Qin Wu1, Yu-Xia Li2, You Zhou2, Zheng-Yu Fang2, Wei Wei1

1Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China

2Institute of Biomedical Research, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China

*First authors

Correspondence to:

Wei Wei, email: rxwei1123@163.com

Zheng-Yu Fang, email: fangzy796@163.com

Keywords: aspirin, ER-positive breast cancer, c-myc, cyclinD1, tamoxifen resistance

Received: December 28, 2016     Accepted: March 09, 2017     Published: March 17, 2017

ABSTRACT

Tamoxifen is still the most commonly used endocrine therapy drug for estrogen receptor (ER)-positive breast cancer patients and has an excellent outcome, but tamoxifen resistance remains a great impediment to successful treatment. Recent studies have prompted an anti-tumor effect of aspirin. Here, we demonstrated that aspirin not only inhibits the growth of ER-positive breast cancer cell line MCF-7, especially when combined with tamoxifen, but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Aspirin combined with tamoxifen can down regulate cyclinD1 and block cell cycle in G0/G1 phase. Besides, tamoxifen alone represses c-myc, progesterone receptor (PR) and cyclinD1 in MCF-7 cell line but not in MCF-7/TAM, while aspirin combined with tamoxifen can inhibit the expression of these proteins in the resistant cell line. When knocking down c-myc in MCF-7/TAM, cells become more sensitive to tamoxifen, cell cycle is blocked as well, indicating that aspirin can regulate c-myc and cyclinD1 proteins to overcome tamoxifen resistance. Our study discovered a novel role of aspirin based on its anti-tumor effect, and put forward some kinds of possible mechanisms of tamoxifen resistance in ER-positive breast cancer cells, providing a new strategy for the treatment of ER-positive breast carcinoma.


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