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Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines
BACKGROUND: Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. ME...
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/PMC4038078/ https://www.ncbi.nlm.nih.gov/pubmed/24885890 http://dx.doi.org/10.1186/1471-2407-14-351 |
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author | D’Alessandro, Rosalba Refolo, Maria G Lippolis, Catia Giannuzzi, Grazia Carella, Nicola Messa, Caterina Cavallini, Aldo Carr, Brian I |
author_facet | D’Alessandro, Rosalba Refolo, Maria G Lippolis, Catia Giannuzzi, Grazia Carella, Nicola Messa, Caterina Cavallini, Aldo Carr, Brian I |
author_sort | D’Alessandro, Rosalba |
collection | PubMed |
description | BACKGROUND: Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. METHODS: Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. RESULTS: Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. CONCLUSIONS: Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions. |
format | Online Article Text |
id | pubmed-4038078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-40380782014-05-30 Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines D’Alessandro, Rosalba Refolo, Maria G Lippolis, Catia Giannuzzi, Grazia Carella, Nicola Messa, Caterina Cavallini, Aldo Carr, Brian I BMC Cancer Research Article BACKGROUND: Platelets are frequently altered in hepatocellular carcinoma (HCC) patients. Platelet lysates (hPL) can enhance HCC cell growth and decrease apoptosis. The aims were to evaluate whether hPL can modulate the actions of Sorafenib or Regorafenib, two clinical HCC multikinase antagonists. METHODS: Several human HCC cell lines were grown in the presence and absence of Sorafenib or Regorafenib, with or without hPL. Growth was measured by MTT assay, apoptosis was assessed by Annexin V and by western blot, and autophagy and MAPK growth signaling were also measured by western blot, and migration and invasion were measured by standard in vitro assays. RESULTS: Both Sorafenib and Regorafenib-mediated inhibition of cell growth, migration and invasion were all antagonized by hPL. Drug-mediated apoptosis and decrease in phospho-ERK levels were both blocked by hPL, which also increased anti-apoptotic phospho-STAT, Bax and Bcl-xL levels. Preliminary data, obtained with epidermal growth factor (EGF) and insulin-like growth factor-I (IGF-I), included in hPL, revealed that these factors were able to antagonized Sorafenib in a proliferation assay, in particular when used in combination. CONCLUSIONS: Platelet factors can antagonize Sorafenib or Regorafenib-mediated growth inhibition and apoptosis in HCC cells. The modulation of platelet activity or numbers has the potential to enhance multikinase drug actions. BioMed Central 2014-05-21 /pmc/articles/PMC4038078/ /pubmed/24885890 http://dx.doi.org/10.1186/1471-2407-14-351 Text en Copyright © 2014 D’Alessandro 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 | Research Article D’Alessandro, Rosalba Refolo, Maria G Lippolis, Catia Giannuzzi, Grazia Carella, Nicola Messa, Caterina Cavallini, Aldo Carr, Brian I Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
title | Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
title_full | Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
title_fullStr | Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
title_full_unstemmed | Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
title_short | Antagonism of Sorafenib and Regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
title_sort | antagonism of sorafenib and regorafenib actions by platelet factors in hepatocellular carcinoma cell lines |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038078/ https://www.ncbi.nlm.nih.gov/pubmed/24885890 http://dx.doi.org/10.1186/1471-2407-14-351 |
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