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Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment
BACKGROUND: Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Br...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984027/ https://www.ncbi.nlm.nih.gov/pubmed/24693884 http://dx.doi.org/10.1186/1475-2867-14-32 |
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author | Zheng, Xiaohui Ding, Ning Song, Yuqin Feng, Lixia Zhu, Jun |
author_facet | Zheng, Xiaohui Ding, Ning Song, Yuqin Feng, Lixia Zhu, Jun |
author_sort | Zheng, Xiaohui |
collection | PubMed |
description | BACKGROUND: Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients. METHODS: The proliferation and apoptosis induction of tumor cells were measured by cell viability assay and Annexin-V staining. Western Blotting analysis and real-time PCR were used to detect the expression level of target proteins and chemokines production. RESULTS: We demonstrated that ibrutinib inhibited the proliferation and induced apoptosis of GCB-DLBCL cell lines through suppression of BCR signaling pathway and activation of caspase-3. Furthermore, the chemokines CCL3 and CCL4 production from tumor cells were also found to be attenuated by ibrutinib treatment. But different cell lines exhibited distinct sensitivity after ibrutinib treatment. Interestingly, the decreasing level of p-ERK after ibrutinib treatment, but not the basal expression level of Btk, correlated with different drug sensitivity. CONCLUSIONS: Ibrutinib could be a potentially useful therapy for GCB-DLBCL and the decreasing level of p-ERK could become a useful biomarker to predict related therapeutic response. |
format | Online Article Text |
id | pubmed-3984027 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39840272014-04-12 Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment Zheng, Xiaohui Ding, Ning Song, Yuqin Feng, Lixia Zhu, Jun Cancer Cell Int Primary Research BACKGROUND: Although rituximab in the combination of CHOP chemotherapy has been widely used as the standard treatment for several kinds of B-cell non-Hodgkin lymphoma (B-NHL), a great number of B-NHL patients treated with this immunotherapy still develop primary and secondary resistance. Recently Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib showed promising therapeutic effect in relapsed/refractory CLL and B-cell NHL, which provided essential alternatives for these patients. METHODS: The proliferation and apoptosis induction of tumor cells were measured by cell viability assay and Annexin-V staining. Western Blotting analysis and real-time PCR were used to detect the expression level of target proteins and chemokines production. RESULTS: We demonstrated that ibrutinib inhibited the proliferation and induced apoptosis of GCB-DLBCL cell lines through suppression of BCR signaling pathway and activation of caspase-3. Furthermore, the chemokines CCL3 and CCL4 production from tumor cells were also found to be attenuated by ibrutinib treatment. But different cell lines exhibited distinct sensitivity after ibrutinib treatment. Interestingly, the decreasing level of p-ERK after ibrutinib treatment, but not the basal expression level of Btk, correlated with different drug sensitivity. CONCLUSIONS: Ibrutinib could be a potentially useful therapy for GCB-DLBCL and the decreasing level of p-ERK could become a useful biomarker to predict related therapeutic response. BioMed Central 2014-04-03 /pmc/articles/PMC3984027/ /pubmed/24693884 http://dx.doi.org/10.1186/1475-2867-14-32 Text en Copyright © 2014 Zheng et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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. |
spellingShingle | Primary Research Zheng, Xiaohui Ding, Ning Song, Yuqin Feng, Lixia Zhu, Jun Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment |
title | Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment |
title_full | Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment |
title_fullStr | Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment |
title_full_unstemmed | Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment |
title_short | Different sensitivity of germinal center B cell-like diffuse large B cell lymphoma cells towards ibrutinib treatment |
title_sort | different sensitivity of germinal center b cell-like diffuse large b cell lymphoma cells towards ibrutinib treatment |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984027/ https://www.ncbi.nlm.nih.gov/pubmed/24693884 http://dx.doi.org/10.1186/1475-2867-14-32 |
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