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

// Ran Cheng 1, * , Ya-Jing Liu 2, * , Jun-Wei Cui 1 , Man Yang 1 , Xiao-Ling Liu 1 , Peng Li 1 , Zhan Wang 1 , Li-Zhang Zhu 1 , Si-Yi Lu 1 , Li Zou 1 , Xiao-Qin Wu 1 , Yu-Xia Li 2 , You Zhou 2 , Zheng-Yu Fang 2 , Wei Wei 1 1 Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, 518036, China 2 Institute 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.