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CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells
Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295386/ https://www.ncbi.nlm.nih.gov/pubmed/27363028 http://dx.doi.org/10.18632/oncotarget.10252 |
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author | Xiong, Lijuan Ding, Li Ning, Haoyong Wu, Chenglin Fu, Kaifei Wang, Yuxiao Zhang, Yan Liu, Yan Zhou, Lijun |
author_facet | Xiong, Lijuan Ding, Li Ning, Haoyong Wu, Chenglin Fu, Kaifei Wang, Yuxiao Zhang, Yan Liu, Yan Zhou, Lijun |
author_sort | Xiong, Lijuan |
collection | PubMed |
description | Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab. |
format | Online Article Text |
id | pubmed-5295386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-52953862017-02-08 CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells Xiong, Lijuan Ding, Li Ning, Haoyong Wu, Chenglin Fu, Kaifei Wang, Yuxiao Zhang, Yan Liu, Yan Zhou, Lijun Oncotarget Research Paper Trastuzumab is widely used in the clinical treatment of human epidermal growth factor receptor-2 (HER2)-positive breast cancer, but the patient response rate is low. CD147 stimulates cancer cell proliferation, migration, metastasis and differentiation and is involved in chemoresistance in many types of cancer cells. Whether CD147 alters the effect of trastuzumab on HER2-positive breast cancer cells has not been previously reported. Our study confirmed that CD147 suppression enhances the effects of trastuzumab both in vitro and in vivo. CD147 suppression increased the inhibitory rate of trastuzumab and cell apoptosis in SKBR3, BT474, HCC1954 and MDA-MB453 cells compared with the controls. Furthermore, CD147 knockdown increased expression of cleaved Caspase-3/9 and poly (ADP-ribose) polymerase (PARP) and decreased both mitogen-activated protein kinase (MAPK) and Akt phosphorylation in the four cell lines. In an HCC1954 xenograft model, trastuzumab achieved greater suppression of tumor growth in the CD147-knockdown group than in the shRNA negative control (NC) group. These data indicated that enhancement of the effect of trastuzumab on HER2-positive cells following CD147 knockdown might be attributed to increased apoptosis and decreased phosphorylation of signaling proteins. CD147 may be a key protein for enhancing the clinical efficacy of trastuzumab. Impact Journals LLC 2016-06-23 /pmc/articles/PMC5295386/ /pubmed/27363028 http://dx.doi.org/10.18632/oncotarget.10252 Text en Copyright: © 2016 Xiong 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 Xiong, Lijuan Ding, Li Ning, Haoyong Wu, Chenglin Fu, Kaifei Wang, Yuxiao Zhang, Yan Liu, Yan Zhou, Lijun CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells |
title | CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells |
title_full | CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells |
title_fullStr | CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells |
title_full_unstemmed | CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells |
title_short | CD147 knockdown improves the antitumor efficacy of trastuzumab in HER2-positive breast cancer cells |
title_sort | cd147 knockdown improves the antitumor efficacy of trastuzumab in her2-positive breast cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295386/ https://www.ncbi.nlm.nih.gov/pubmed/27363028 http://dx.doi.org/10.18632/oncotarget.10252 |
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