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Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells

Everolimus inhibits mammalian target of rapamycin (mTOR) and leads to decreased protein synthesis and decreased cancer cell proliferation in many experimental systems. Adenosine 5′-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC...

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Autores principales: Wang, Yunshan, Wei, Junmin, Li, Li, Fan, Cong, Sun, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cognizant Communication Corporation 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838426/
https://www.ncbi.nlm.nih.gov/pubmed/26351208
http://dx.doi.org/10.3727/096504015X14348950540999
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author Wang, Yunshan
Wei, Junmin
Li, Li
Fan, Cong
Sun, Ying
author_facet Wang, Yunshan
Wei, Junmin
Li, Li
Fan, Cong
Sun, Ying
author_sort Wang, Yunshan
collection PubMed
description Everolimus inhibits mammalian target of rapamycin (mTOR) and leads to decreased protein synthesis and decreased cancer cell proliferation in many experimental systems. Adenosine 5′-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Histopathological and biochemical studies of breast cancer show frequent dysregulation of the AMPK and the mTOR pathway. Therefore, we investigated the efficacy of the mTOR inhibitor everolimus and metformin in the treatment of breast cancer cells. This study evaluated the in vitro and in vivo effects of everolimus alone or in combination with metformin on breast cancer cells. MTT assay was used to quantify the inhibitory effect of the drugs on breast cancer cells in vitro. SCID mice injected with HCC1428 cells followed by different treatments were used to assess the in vivo efficacy of different agents. Data showed that the combination of everolimus and metformin exerted synergistic inhibitory effects on the growth of breast cancer cells both in culture and in a mouse xenograft model. Further, this combination abrogated S6 and 4EBP1phosphorylation. Collectively, we suggest that the combination of everolimus and metformin may be an effective regimen for treatment of breast cancer, hence warranting further evaluation of the combination in the clinic.
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spelling pubmed-78384262021-02-16 Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells Wang, Yunshan Wei, Junmin Li, Li Fan, Cong Sun, Ying Oncol Res Article Everolimus inhibits mammalian target of rapamycin (mTOR) and leads to decreased protein synthesis and decreased cancer cell proliferation in many experimental systems. Adenosine 5′-monophosphate-activated protein kinase (AMPK) activators such as metformin have similar actions in keeping with the TSC2/1 pathway linking activation of AMPK to inhibition of mTOR. Histopathological and biochemical studies of breast cancer show frequent dysregulation of the AMPK and the mTOR pathway. Therefore, we investigated the efficacy of the mTOR inhibitor everolimus and metformin in the treatment of breast cancer cells. This study evaluated the in vitro and in vivo effects of everolimus alone or in combination with metformin on breast cancer cells. MTT assay was used to quantify the inhibitory effect of the drugs on breast cancer cells in vitro. SCID mice injected with HCC1428 cells followed by different treatments were used to assess the in vivo efficacy of different agents. Data showed that the combination of everolimus and metformin exerted synergistic inhibitory effects on the growth of breast cancer cells both in culture and in a mouse xenograft model. Further, this combination abrogated S6 and 4EBP1phosphorylation. Collectively, we suggest that the combination of everolimus and metformin may be an effective regimen for treatment of breast cancer, hence warranting further evaluation of the combination in the clinic. Cognizant Communication Corporation 2015-09-15 /pmc/articles/PMC7838426/ /pubmed/26351208 http://dx.doi.org/10.3727/096504015X14348950540999 Text en Copyright © 2015 Cognizant Comm. Corp. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License.
spellingShingle Article
Wang, Yunshan
Wei, Junmin
Li, Li
Fan, Cong
Sun, Ying
Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells
title Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells
title_full Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells
title_fullStr Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells
title_full_unstemmed Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells
title_short Combined Use of Metformin and Everolimus Is Synergistic in the Treatment of Breast Cancer Cells
title_sort combined use of metformin and everolimus is synergistic in the treatment of breast cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838426/
https://www.ncbi.nlm.nih.gov/pubmed/26351208
http://dx.doi.org/10.3727/096504015X14348950540999
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