Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma.
Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma.
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二甲双胍增强他莫昔芬介导的 ER 阳性乳腺癌肿瘤生长抑制
DOI：
10.1186/1471-2407-14-172
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发表时间：
2014-03-11
期刊：
影响因子：
3.8
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Ma J;Guo Y;Chen S;Zhong C;Xue Y;Zhang Y;Lai X;Wei Y;Yu S;Zhang J;Liu W
研究背景他莫昔芬是一种治疗乳腺癌的内分泌治疗药物，其作用是通过阻断雌激素受体（ER）来阻断雌激素信号传导。然而，许多ER阳性患者对他莫昔芬反应性低或耐药。二甲双胍是一种广泛使用的抗糖尿病药物，具有显著的抗癌作用。我们调查了二甲双胍是否具有与他莫昔芬在ER阳性breast cancer therapeutic.MethodsThe二甲双胍单独和与他莫昔芬联合对ER阳性乳腺癌的疗效进行了分析，通过细胞存活率，DNA复制活性，平板集落形成，软琼脂，流式细胞术，免疫组化和裸鼠模型测定。结果二甲双胍与三苯氧胺联用时，抑制细胞生长所需的三苯氧胺浓度显著降低。此外，二甲双胍增强了他莫昔芬介导的ER阳性乳腺癌细胞增殖抑制、DNA复制活性、集落形成、软琼脂集落形成和凋亡诱导。此外，二甲双胍增强的这些他莫昔芬诱导的作用可能涉及bax/bcl-2凋亡途径和AMPK/mTOR/p70 S6生长途径。最后，两种药物联合治疗显着抑制肿瘤生长在vivo.ConclusionThe目前的工作表明，二甲双胍和他莫昔芬添加抑制ER阳性乳腺癌细胞的生长和增强凋亡。它为将来研究这种药物组合治疗ER阳性乳腺癌提供了线索。
BackgroundTamoxifen, 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.MethodsThe 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.ResultsWhen 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.ConclusionThe present work shows that metformin and tamoxifen additively inhibited the growth and augmented the apoptosis of ER-positive breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer.
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影响因子：
168.9
作者：
Davies, Christina;Pan, Hongchao;Godwin, Jon;Gray, Richard;Arriagada, Rodrigo;Raina, Vinod;Abraham, Mirta;Medeiros Alencar, Victor Hugo;Badran, Atef;Bonfill, Xavier;Bradbury, Joan;Clarke, Michael;Collins, Rory;Davis, Susan R.;Delmestri, Antonella;Forbes, John F.;Haddad, Peiman;Hou, Ming-Feng;Inbar, Moshe;Khaled, Hussein;Kielanowska, Joanna;Kwan, Wing-Hong;Mathew, Beela S.;Mittra, Indraneel;Mueller, Bettina;Nicolucci, Antonio;Peralta, Octavio;Pernas, Fany;Petruzelka, Lubos;Pienkowski, Tadeusz;Radhika, Ramachandran;Rajan, Balakrishnan;Rubach, Maryna T.;Tort, Sera;Urrutia, Gerard;Valentini, Miriam;Wang, Yaochen;Peto, Richard
通讯作者：
Peto, Richard
DOI：
10.3109/08977194.2011.565003
发表时间：
2011-04
期刊：
Growth factors (Chur, Switzerland)
影响因子：
--
作者：
Richardson AE;Hamilton N;Davis W;Brito C;De León D
通讯作者：
De León D
影响因子：
45.3
作者：
Jiralerspong, Sao;Palla, Shana L.;Gonzalez-Angulo, Ana M.
通讯作者：
Gonzalez-Angulo, Ana M.
影响因子：
45.3
作者：
Bachelot, Thomas;Bourgier, Celine;Pujade-Lauraine, Eric
通讯作者：
Pujade-Lauraine, Eric
影响因子：
3.8
作者：
Niraula, Saroj;Dowling, Ryan J. O.;Goodwin, Pamela J.
通讯作者：
Goodwin, Pamela J.