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Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2

Pre-clinical and on-going trials have indicated the advantage of using metformin as an anticancer drug alone or in combination with other chemotherapeutics for the treatment of patients with breast cancer. However, the mechanisms by which metformin attenuates tumorigenesis remain to be further eluci...

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Autores principales: Shi, Bin, Hu, Xinyu, He, Huimin, Fang, Wenzheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243079/
https://www.ncbi.nlm.nih.gov/pubmed/34257723
http://dx.doi.org/10.3892/ol.2021.12876
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author Shi, Bin
Hu, Xinyu
He, Huimin
Fang, Wenzheng
author_facet Shi, Bin
Hu, Xinyu
He, Huimin
Fang, Wenzheng
author_sort Shi, Bin
collection PubMed
description Pre-clinical and on-going trials have indicated the advantage of using metformin as an anticancer drug alone or in combination with other chemotherapeutics for the treatment of patients with breast cancer. However, the mechanisms by which metformin attenuates tumorigenesis remain to be further elucidated. The present study investigated the anticancer effects of metformin in breast cancer and identified potential molecular targets of metformin using western blotting and immunohistochemical analysis. Metformin significantly decreased tumor cell proliferation in vitro and suppressed tumor growth in vivo. Moreover, it induced the activation of AMP-induced protein kinase and suppression of phosphorylated-eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1), a downstream effector of the mTOR signaling pathway, and decreased cyclin D1 levels in in vitro and in vivo experimental models. Additionally, metformin inhibited cyclooxygenase (COX)-2 expression. Clinically, high expression levels of COX-2 and p-4E-BP1 in tissues of patients with breast cancer were significantly associated with enhanced lymphatic metastasis and distant metastasis. Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways.
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spelling pubmed-82430792021-07-12 Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2 Shi, Bin Hu, Xinyu He, Huimin Fang, Wenzheng Oncol Lett Articles Pre-clinical and on-going trials have indicated the advantage of using metformin as an anticancer drug alone or in combination with other chemotherapeutics for the treatment of patients with breast cancer. However, the mechanisms by which metformin attenuates tumorigenesis remain to be further elucidated. The present study investigated the anticancer effects of metformin in breast cancer and identified potential molecular targets of metformin using western blotting and immunohistochemical analysis. Metformin significantly decreased tumor cell proliferation in vitro and suppressed tumor growth in vivo. Moreover, it induced the activation of AMP-induced protein kinase and suppression of phosphorylated-eukaryotic translation initiation factor 4E-binding protein 1 (p-4E-BP1), a downstream effector of the mTOR signaling pathway, and decreased cyclin D1 levels in in vitro and in vivo experimental models. Additionally, metformin inhibited cyclooxygenase (COX)-2 expression. Clinically, high expression levels of COX-2 and p-4E-BP1 in tissues of patients with breast cancer were significantly associated with enhanced lymphatic metastasis and distant metastasis. Thus, the current data suggested that metformin may have potential value as a synergistic therapy targeting both the COX-2 and mTOR signaling pathways. D.A. Spandidos 2021-08 2021-06-23 /pmc/articles/PMC8243079/ /pubmed/34257723 http://dx.doi.org/10.3892/ol.2021.12876 Text en Copyright: © Shi et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Shi, Bin
Hu, Xinyu
He, Huimin
Fang, Wenzheng
Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
title Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
title_full Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
title_fullStr Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
title_full_unstemmed Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
title_short Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
title_sort metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243079/
https://www.ncbi.nlm.nih.gov/pubmed/34257723
http://dx.doi.org/10.3892/ol.2021.12876
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