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Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer
PURPOSE: Berberine (BBR), a traditional Chinese medicine, has been shown effects on inhibiting cancer development. Autophagy-mediated resistance plays an important role in cancer progression; therefore, regulation of autophagy is a novel therapeutic strategy for cancer treatment. However, effects of...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061433/ https://www.ncbi.nlm.nih.gov/pubmed/32184626 http://dx.doi.org/10.2147/OTT.S241632 |
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author | Wang, Ye Liu, Yanfang Du, Xinyang Ma, Hong Yao, Jing |
author_facet | Wang, Ye Liu, Yanfang Du, Xinyang Ma, Hong Yao, Jing |
author_sort | Wang, Ye |
collection | PubMed |
description | PURPOSE: Berberine (BBR), a traditional Chinese medicine, has been shown effects on inhibiting cancer development. Autophagy-mediated resistance plays an important role in cancer progression; therefore, regulation of autophagy is a novel therapeutic strategy for cancer treatment. However, effects of BBR on autophagy-mediated resistance have not been reported. METHODS: MCF-7 breast cancer cells and the doxorubicin (ADR)-resistant MCF-7 cells (MCF-7/ADR) were used for analyses. Western blotting was conducted to evaluate protein expression; MTT, colony formation, and EdU assays were conducted to assess cell proliferation; transmission electron microscopy was used to monitor autophagy levels; and a xenograft tumor model was established to assess the effects of BBR on reversing doxorubicin resistance. RESULTS: We confirmed that BBR, recently identified as a suppressor of autophagy, inhibits autophagosome formation in MCF-7/ADR cells. Treatment with BBR blocked the accumulation of the autophagy-associated protein LC3II, resulting in cellular accumulation of p62, reduced cell proliferation, and reversal of doxorubicin resistance. Mechanistically, we found that BBR inhibited autophagy by modulating the PTEN/Akt/mTOR signaling pathway. In vivo, our study showed that BBR exerts clear anti-tumor effects. CONCLUSION: The results of this study suggest that BBR reverses doxorubicin resistance in breast cancer cells by inhibiting autophagy. This finding highlights the potential clinical application of BBR in the treatment of breast cancer. |
format | Online Article Text |
id | pubmed-7061433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-70614332020-03-17 Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer Wang, Ye Liu, Yanfang Du, Xinyang Ma, Hong Yao, Jing Onco Targets Ther Original Research PURPOSE: Berberine (BBR), a traditional Chinese medicine, has been shown effects on inhibiting cancer development. Autophagy-mediated resistance plays an important role in cancer progression; therefore, regulation of autophagy is a novel therapeutic strategy for cancer treatment. However, effects of BBR on autophagy-mediated resistance have not been reported. METHODS: MCF-7 breast cancer cells and the doxorubicin (ADR)-resistant MCF-7 cells (MCF-7/ADR) were used for analyses. Western blotting was conducted to evaluate protein expression; MTT, colony formation, and EdU assays were conducted to assess cell proliferation; transmission electron microscopy was used to monitor autophagy levels; and a xenograft tumor model was established to assess the effects of BBR on reversing doxorubicin resistance. RESULTS: We confirmed that BBR, recently identified as a suppressor of autophagy, inhibits autophagosome formation in MCF-7/ADR cells. Treatment with BBR blocked the accumulation of the autophagy-associated protein LC3II, resulting in cellular accumulation of p62, reduced cell proliferation, and reversal of doxorubicin resistance. Mechanistically, we found that BBR inhibited autophagy by modulating the PTEN/Akt/mTOR signaling pathway. In vivo, our study showed that BBR exerts clear anti-tumor effects. CONCLUSION: The results of this study suggest that BBR reverses doxorubicin resistance in breast cancer cells by inhibiting autophagy. This finding highlights the potential clinical application of BBR in the treatment of breast cancer. Dove 2020-03-04 /pmc/articles/PMC7061433/ /pubmed/32184626 http://dx.doi.org/10.2147/OTT.S241632 Text en © 2020 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). |
spellingShingle | Original Research Wang, Ye Liu, Yanfang Du, Xinyang Ma, Hong Yao, Jing Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer |
title | Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer |
title_full | Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer |
title_fullStr | Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer |
title_full_unstemmed | Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer |
title_short | Berberine Reverses Doxorubicin Resistance by Inhibiting Autophagy Through the PTEN/Akt/mTOR Signaling Pathway in Breast Cancer |
title_sort | berberine reverses doxorubicin resistance by inhibiting autophagy through the pten/akt/mtor signaling pathway in breast cancer |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7061433/ https://www.ncbi.nlm.nih.gov/pubmed/32184626 http://dx.doi.org/10.2147/OTT.S241632 |
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