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Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma
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 notewort...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976359/ https://www.ncbi.nlm.nih.gov/pubmed/24612549 http://dx.doi.org/10.1186/1471-2407-14-172 |
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author | Ma, Ji Guo, Yan Chen, Suning Zhong, Cuiping Xue, Yan Zhang, Yuan Lai, Xiaofeng Wei, Yifang Yu, Shentong Zhang, Jian Liu, Wenchao |
author_facet | Ma, Ji Guo, Yan Chen, Suning Zhong, Cuiping Xue, Yan Zhang, Yuan Lai, Xiaofeng Wei, Yifang Yu, Shentong Zhang, Jian Liu, Wenchao |
author_sort | Ma, Ji |
collection | PubMed |
description | 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 breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer. |
format | Online Article Text |
id | pubmed-3976359 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39763592014-04-05 Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma Ma, Ji Guo, Yan Chen, Suning Zhong, Cuiping Xue, Yan Zhang, Yuan Lai, Xiaofeng Wei, Yifang Yu, Shentong Zhang, Jian Liu, Wenchao BMC Cancer Research Article 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 breast cancer cells. It provides leads for future research on this drug combination for the treatment of ER-positive breast cancer. BioMed Central 2014-03-11 /pmc/articles/PMC3976359/ /pubmed/24612549 http://dx.doi.org/10.1186/1471-2407-14-172 Text en Copyright © 2014 Ma et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Ma, Ji Guo, Yan Chen, Suning Zhong, Cuiping Xue, Yan Zhang, Yuan Lai, Xiaofeng Wei, Yifang Yu, Shentong Zhang, Jian Liu, Wenchao Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma |
title | Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma |
title_full | Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma |
title_fullStr | Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma |
title_full_unstemmed | Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma |
title_short | Metformin enhances tamoxifen-mediated tumor growth inhibition in ER-positive breast carcinoma |
title_sort | metformin enhances tamoxifen-mediated tumor growth inhibition in er-positive breast carcinoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976359/ https://www.ncbi.nlm.nih.gov/pubmed/24612549 http://dx.doi.org/10.1186/1471-2407-14-172 |
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