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Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3
BACKGROUND: Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian canc...
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/PMC4260252/ https://www.ncbi.nlm.nih.gov/pubmed/25424625 http://dx.doi.org/10.1186/s13048-014-0103-5 |
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author | Wang, Wei Zhang, Yan Lv, Ming Feng, Jiannan Peng, Hui Geng, Jing Lin, Zhou Zhou, Tingting Li, Xinying Shen, Beifen Ma, Yuanfang Qiao, Chunxia |
author_facet | Wang, Wei Zhang, Yan Lv, Ming Feng, Jiannan Peng, Hui Geng, Jing Lin, Zhou Zhou, Tingting Li, Xinying Shen, Beifen Ma, Yuanfang Qiao, Chunxia |
author_sort | Wang, Wei |
collection | PubMed |
description | BACKGROUND: Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival. METHODS: IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1R monoclonal antibody, named as LMAb1, was used to inhibit SKOV3-T in cell growth/proliferation, migration, clone formation and in vivo carcinogenicity. RESULTS: In both in vitro and in vivo assays, LMAb1 showed effective anti-tumor function, especially when being used in combination with trastuzumab, which was beneficial to longer survival time of mice as well as smaller tumor. It was also confirmed preliminarily that the mechanism of antibody might be to inhibit the activation of IGF-1R and downstream MAPK, AKT pathway transduction. CONCLUSION: We achieved satisfactory anti-tumor activity using trastuzumab plus LMAb1 in trastuzumab-resistant ovarian cancer model. In similar cases, not only acquired but also de novo, good curative effect might be achieved using combined antibody therapy strategies. |
format | Online Article Text |
id | pubmed-4260252 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42602522014-12-09 Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 Wang, Wei Zhang, Yan Lv, Ming Feng, Jiannan Peng, Hui Geng, Jing Lin, Zhou Zhou, Tingting Li, Xinying Shen, Beifen Ma, Yuanfang Qiao, Chunxia J Ovarian Res Research BACKGROUND: Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival. METHODS: IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1R monoclonal antibody, named as LMAb1, was used to inhibit SKOV3-T in cell growth/proliferation, migration, clone formation and in vivo carcinogenicity. RESULTS: In both in vitro and in vivo assays, LMAb1 showed effective anti-tumor function, especially when being used in combination with trastuzumab, which was beneficial to longer survival time of mice as well as smaller tumor. It was also confirmed preliminarily that the mechanism of antibody might be to inhibit the activation of IGF-1R and downstream MAPK, AKT pathway transduction. CONCLUSION: We achieved satisfactory anti-tumor activity using trastuzumab plus LMAb1 in trastuzumab-resistant ovarian cancer model. In similar cases, not only acquired but also de novo, good curative effect might be achieved using combined antibody therapy strategies. BioMed Central 2014-11-26 /pmc/articles/PMC4260252/ /pubmed/25424625 http://dx.doi.org/10.1186/s13048-014-0103-5 Text en © Wang et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), 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 | Research Wang, Wei Zhang, Yan Lv, Ming Feng, Jiannan Peng, Hui Geng, Jing Lin, Zhou Zhou, Tingting Li, Xinying Shen, Beifen Ma, Yuanfang Qiao, Chunxia Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 |
title | Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 |
title_full | Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 |
title_fullStr | Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 |
title_full_unstemmed | Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 |
title_short | Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3 |
title_sort | anti-igf-1r monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant skov3 |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260252/ https://www.ncbi.nlm.nih.gov/pubmed/25424625 http://dx.doi.org/10.1186/s13048-014-0103-5 |
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