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Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma

BACKGROUND: The ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-re...

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Autores principales: Qu, Huiling, Song, Xiaofu, Song, Zhuyin, Jiang, Xin, Gao, Xin, Bai, Lijuan, Wu, Jiao, Na, Li, Yao, Zhicheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727240/
https://www.ncbi.nlm.nih.gov/pubmed/33298057
http://dx.doi.org/10.1186/s12935-020-01693-y
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author Qu, Huiling
Song, Xiaofu
Song, Zhuyin
Jiang, Xin
Gao, Xin
Bai, Lijuan
Wu, Jiao
Na, Li
Yao, Zhicheng
author_facet Qu, Huiling
Song, Xiaofu
Song, Zhuyin
Jiang, Xin
Gao, Xin
Bai, Lijuan
Wu, Jiao
Na, Li
Yao, Zhicheng
author_sort Qu, Huiling
collection PubMed
description BACKGROUND: The ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-resistant cell lines to mimic a physiologically relevant GBM experimental system. METHODS: By treating these resistant cell lines with berberine followed by TMZ, we were able to assess the chemosensitivity of these cells and their parental strains, based on their performance in the MTT and colony formation assays, as well as on the degree of detectable apoptosis that was detected in the strains. Furthermore, we used Western blotting to assess autophagic responses in these cell lines, and we extended this work into a xenograft mouse model to assess the in vivo efficacy of berberine. RESULTS: Through these experiments, our findings indicated that berberine enhanced autophagy and apoptosis in TMZ-resistant cells upon TMZ treatment in a manner that was linked with ERK1/2 signaling. Similarly, when used in vivo, berberine increased GBM sensitivity to TMZ through ERK1/2 signaling pathways. CONCLUSIONS: These findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment.
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spelling pubmed-77272402020-12-11 Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma Qu, Huiling Song, Xiaofu Song, Zhuyin Jiang, Xin Gao, Xin Bai, Lijuan Wu, Jiao Na, Li Yao, Zhicheng Cancer Cell Int Primary Research BACKGROUND: The ability to treat glioblastoma (GBM) using the chemotherapeutic agent temozolomide (TMZ) has been hampered by the development of therapeutic resistance. In this study, we assessed the ability of the isoquinoline alkaloid berberine to alter GBM TMZ resistance using two different TMZ-resistant cell lines to mimic a physiologically relevant GBM experimental system. METHODS: By treating these resistant cell lines with berberine followed by TMZ, we were able to assess the chemosensitivity of these cells and their parental strains, based on their performance in the MTT and colony formation assays, as well as on the degree of detectable apoptosis that was detected in the strains. Furthermore, we used Western blotting to assess autophagic responses in these cell lines, and we extended this work into a xenograft mouse model to assess the in vivo efficacy of berberine. RESULTS: Through these experiments, our findings indicated that berberine enhanced autophagy and apoptosis in TMZ-resistant cells upon TMZ treatment in a manner that was linked with ERK1/2 signaling. Similarly, when used in vivo, berberine increased GBM sensitivity to TMZ through ERK1/2 signaling pathways. CONCLUSIONS: These findings demonstrate that berberine is an effective method of increasing the sensitization of GBM cells to TMZ treatment in a manner that is dependent upon the ERK1/2-mediated induction of autophagy, thus making berberine a potentially viable therapeutic agent for GBM treatment. BioMed Central 2020-12-09 /pmc/articles/PMC7727240/ /pubmed/33298057 http://dx.doi.org/10.1186/s12935-020-01693-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Primary Research
Qu, Huiling
Song, Xiaofu
Song, Zhuyin
Jiang, Xin
Gao, Xin
Bai, Lijuan
Wu, Jiao
Na, Li
Yao, Zhicheng
Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma
title Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma
title_full Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma
title_fullStr Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma
title_full_unstemmed Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma
title_short Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma
title_sort berberine reduces temozolomide resistance by inducing autophagy via the erk1/2 signaling pathway in glioblastoma
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727240/
https://www.ncbi.nlm.nih.gov/pubmed/33298057
http://dx.doi.org/10.1186/s12935-020-01693-y
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