TY - JOUR
AU1 - Ma, Ji
AU2 - Guo, Yan
AU3 - Chen, Suning
AU4 - Zhong, Cuiping
AU5 - Xue, Yan
AU6 - Zhang, Yuan
AU7 - Lai, Xiaofeng
AU8 - Wei, Yifang
AU9 - Yu, Shentong
AU1 - Zhang, Jian
AU1 - Liu, Wenchao
AB - Background: Tamoxifen, an endocrine therapy drug used to treat breast cancer, is designed to interrupt estrogen signaling by blocking the estrogen receptor (ER). However, many ER-positive patients are low reactive or resistant to tamoxifen. Metformin is a widely used anti-diabetic drug with noteworthy anti-cancer effects. We investigated whether metformin has the additive effects with tamoxifen in ER-positive breast cancer therapy. Methods: The efficacy of metformin alone and in combination with tamoxifen against ER-positive breast cancer was analyzed by cell survival, DNA replication activity, plate colony formation, soft-agar, flow cytometry, immunohistochemistry, and nude mice model assays. The involved signaling pathways were detected by western blot assay. Results: When metformin was combined with tamoxifen, the concentration of tamoxifen required for growth inhibition was substantially reduced. Moreover, metformin enhanced tamoxifen-mediated inhibition of proliferation, DNA replication activity, colony formation, soft-agar colony formation, and induction of apoptosis in ER-positive breast cancer cells. In addition, these tamoxifen-induced effects that were enhanced by metformin may be involved in the bax/bcl-2 apoptotic pathway and the AMPK/mTOR/p70S6 growth pathway. Finally, two-drug combination therapy significantly inhibited tumor growth in vivo. Conclusion: The present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive 
TI - Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma
JF - BMC Cancer
DO - 10.1186/1471-2407-14-172
DA - 2014-03-11
UR - https://www.deepdyve.com/lp/springer-journals/metformin-enhances-tamoxifen-mediated-tumor-growth-inhibition-in-er-26DZyECvaf
SP - 1
EP - 11
VL - 14
IS - 1
DP - DeepDyve
ER -