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Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis

BACKGROUND: Delanzomib, a novel proteasome inhibitor, has demonstrated promising efficacy and antitumor ability in human multiple myeloma cell lines and patient‐derived cells. However, the potential therapeutic effects of delanzomib on breast cancer remain unknown. In this study, we show that delanz...

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Autores principales: Wang, Mopei, Liang, Li, Lu, Jiaxiong, Yu, Yang, Zhao, Yanling, Shi, Zhenfeng, Li, Hui, Xu, Xin, Yan, Yuxian, Niu, Yan, Liu, Zhentao, Shen, Lin, Zhang, Hong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449274/
https://www.ncbi.nlm.nih.gov/pubmed/30883017
http://dx.doi.org/10.1111/1759-7714.13030
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author Wang, Mopei
Liang, Li
Lu, Jiaxiong
Yu, Yang
Zhao, Yanling
Shi, Zhenfeng
Li, Hui
Xu, Xin
Yan, Yuxian
Niu, Yan
Liu, Zhentao
Shen, Lin
Zhang, Hong
author_facet Wang, Mopei
Liang, Li
Lu, Jiaxiong
Yu, Yang
Zhao, Yanling
Shi, Zhenfeng
Li, Hui
Xu, Xin
Yan, Yuxian
Niu, Yan
Liu, Zhentao
Shen, Lin
Zhang, Hong
author_sort Wang, Mopei
collection PubMed
description BACKGROUND: Delanzomib, a novel proteasome inhibitor, has demonstrated promising efficacy and antitumor ability in human multiple myeloma cell lines and patient‐derived cells. However, the potential therapeutic effects of delanzomib on breast cancer remain unknown. In this study, we show that delanzomib has antitumor effects and synergizes with doxorubicin (Dox) in human breast cancer cell lines. METHODS: Cell proliferation assay and flow cytometry were used to evaluate cell viability and apoptosis in eight human breast cancer cell lines after treatment with delanzomib or Dox. Essential molecules of the p53, MAPK, and apoptosis signaling pathways were analyzed by Western blotting. RESULTS: Delanzomib induced cell death and demonstrated synergism with Dox in all tested breast cancer cell lines. In addition, delanzomib enhanced the Dox‐induced phosphorylation of p38/JNK and the expression of transcriptional target proteins of p53, such as p21, p27, NOXA, and PUMA. CONCLUSION: The combined regimen of the proteasome inhibitor delanzomib with Dox chemotherapy may become an effective strategy for breast cancer therapy.
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spelling pubmed-64492742019-04-15 Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis Wang, Mopei Liang, Li Lu, Jiaxiong Yu, Yang Zhao, Yanling Shi, Zhenfeng Li, Hui Xu, Xin Yan, Yuxian Niu, Yan Liu, Zhentao Shen, Lin Zhang, Hong Thorac Cancer Original Articles BACKGROUND: Delanzomib, a novel proteasome inhibitor, has demonstrated promising efficacy and antitumor ability in human multiple myeloma cell lines and patient‐derived cells. However, the potential therapeutic effects of delanzomib on breast cancer remain unknown. In this study, we show that delanzomib has antitumor effects and synergizes with doxorubicin (Dox) in human breast cancer cell lines. METHODS: Cell proliferation assay and flow cytometry were used to evaluate cell viability and apoptosis in eight human breast cancer cell lines after treatment with delanzomib or Dox. Essential molecules of the p53, MAPK, and apoptosis signaling pathways were analyzed by Western blotting. RESULTS: Delanzomib induced cell death and demonstrated synergism with Dox in all tested breast cancer cell lines. In addition, delanzomib enhanced the Dox‐induced phosphorylation of p38/JNK and the expression of transcriptional target proteins of p53, such as p21, p27, NOXA, and PUMA. CONCLUSION: The combined regimen of the proteasome inhibitor delanzomib with Dox chemotherapy may become an effective strategy for breast cancer therapy. John Wiley & Sons Australia, Ltd 2019-03-18 2019-04 /pmc/articles/PMC6449274/ /pubmed/30883017 http://dx.doi.org/10.1111/1759-7714.13030 Text en © 2019 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Wang, Mopei
Liang, Li
Lu, Jiaxiong
Yu, Yang
Zhao, Yanling
Shi, Zhenfeng
Li, Hui
Xu, Xin
Yan, Yuxian
Niu, Yan
Liu, Zhentao
Shen, Lin
Zhang, Hong
Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
title Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
title_full Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
title_fullStr Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
title_full_unstemmed Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
title_short Delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
title_sort delanzomib, a novel proteasome inhibitor, sensitizes breast cancer cells to doxorubicin‐induced apoptosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6449274/
https://www.ncbi.nlm.nih.gov/pubmed/30883017
http://dx.doi.org/10.1111/1759-7714.13030
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