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Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy
Our previous studies showed that anti-β(2)M monoclonal antibodies (mAbs) have strong and direct apoptotic effects on multiple myeloma (MM) cells, suggesting that anti-β(2)M mAbs might be developed as a novel therapeutic agent. In this study, we investigated the anti-MM effects of combination treatme...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496167/ https://www.ncbi.nlm.nih.gov/pubmed/25895124 |
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author | Zhang, Mingjun He, Jin Liu, Zhiqiang Lu, Yong Zheng, Yuhuan Li, Haiyan Xu, Jingda Liu, Huan Qian, Jianfei Orlowski, Robert Z. Kwak, Larry W. Yi, Qing Yang, Jing |
author_facet | Zhang, Mingjun He, Jin Liu, Zhiqiang Lu, Yong Zheng, Yuhuan Li, Haiyan Xu, Jingda Liu, Huan Qian, Jianfei Orlowski, Robert Z. Kwak, Larry W. Yi, Qing Yang, Jing |
author_sort | Zhang, Mingjun |
collection | PubMed |
description | Our previous studies showed that anti-β(2)M monoclonal antibodies (mAbs) have strong and direct apoptotic effects on multiple myeloma (MM) cells, suggesting that anti-β(2)M mAbs might be developed as a novel therapeutic agent. In this study, we investigated the anti-MM effects of combination treatment with anti-β(2)M mAbs and bortezomib (BTZ). Our results showed that anti-β(2)M mAbs enhanced BTZ-induced apoptosis of MM cell lines and primary MM cells. Combination treatment could also induce apoptosis of BTZ-resistant MM cells, and the enhanced effect depended on the surface expression of β(2)M on MM cells. BTZ up-regulated the expression of autophagy proteins, whereas combination with anti-β(2)M mAbs inhibited autophagy. Sequence analysis of the promoter region of beclin 1 identified 3 putative NF-κB-binding sites from –615 to –789 bp. BTZ treatment increased, whereas combination with anti-β(2)M mAbs reduced, NF-κB transcription activities in MM cells, and combination treatment inhibited NF-κB p65 binding to the beclin 1 promoter. Furthermore, anti-β(2)M mAbs and BTZ combination treatment had anti-MM activities in an established MM mouse model. Thus, our studies provide new insight and support for the clinical development of an anti-β(2)M mAb and BTZ combination treatment to overcome BTZ drug resistance and improve MM patient survival. |
format | Online Article Text |
id | pubmed-4496167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-44961672015-07-10 Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy Zhang, Mingjun He, Jin Liu, Zhiqiang Lu, Yong Zheng, Yuhuan Li, Haiyan Xu, Jingda Liu, Huan Qian, Jianfei Orlowski, Robert Z. Kwak, Larry W. Yi, Qing Yang, Jing Oncotarget Research Paper Our previous studies showed that anti-β(2)M monoclonal antibodies (mAbs) have strong and direct apoptotic effects on multiple myeloma (MM) cells, suggesting that anti-β(2)M mAbs might be developed as a novel therapeutic agent. In this study, we investigated the anti-MM effects of combination treatment with anti-β(2)M mAbs and bortezomib (BTZ). Our results showed that anti-β(2)M mAbs enhanced BTZ-induced apoptosis of MM cell lines and primary MM cells. Combination treatment could also induce apoptosis of BTZ-resistant MM cells, and the enhanced effect depended on the surface expression of β(2)M on MM cells. BTZ up-regulated the expression of autophagy proteins, whereas combination with anti-β(2)M mAbs inhibited autophagy. Sequence analysis of the promoter region of beclin 1 identified 3 putative NF-κB-binding sites from –615 to –789 bp. BTZ treatment increased, whereas combination with anti-β(2)M mAbs reduced, NF-κB transcription activities in MM cells, and combination treatment inhibited NF-κB p65 binding to the beclin 1 promoter. Furthermore, anti-β(2)M mAbs and BTZ combination treatment had anti-MM activities in an established MM mouse model. Thus, our studies provide new insight and support for the clinical development of an anti-β(2)M mAb and BTZ combination treatment to overcome BTZ drug resistance and improve MM patient survival. Impact Journals LLC 2015-03-31 /pmc/articles/PMC4496167/ /pubmed/25895124 Text en Copyright: © 2015 Zhang et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Zhang, Mingjun He, Jin Liu, Zhiqiang Lu, Yong Zheng, Yuhuan Li, Haiyan Xu, Jingda Liu, Huan Qian, Jianfei Orlowski, Robert Z. Kwak, Larry W. Yi, Qing Yang, Jing Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
title | Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
title_full | Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
title_fullStr | Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
title_full_unstemmed | Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
title_short | Anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
title_sort | anti-β(2)-microglobulin monoclonal antibodies overcome bortezomib resistance in multiple myeloma by inhibiting autophagy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496167/ https://www.ncbi.nlm.nih.gov/pubmed/25895124 |
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