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Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma
Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Diversity Preservation International (MDPI)
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756352/ https://www.ncbi.nlm.nih.gov/pubmed/24212609 http://dx.doi.org/10.3390/cancers3010106 |
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author | Hagmann, Wolfgang Faissner, Ralf Schnolzer, Martina Lohr, Matthias Jesnowski, Ralf |
author_facet | Hagmann, Wolfgang Faissner, Ralf Schnolzer, Martina Lohr, Matthias Jesnowski, Ralf |
author_sort | Hagmann, Wolfgang |
collection | PubMed |
description | Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5-overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil. |
format | Online Article Text |
id | pubmed-3756352 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Molecular Diversity Preservation International (MDPI) |
record_format | MEDLINE/PubMed |
spelling | pubmed-37563522013-09-04 Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma Hagmann, Wolfgang Faissner, Ralf Schnolzer, Martina Lohr, Matthias Jesnowski, Ralf Cancers (Basel) Review Pancreatic cancer ranks among the tumors most resistant to chemotherapy. Such chemoresistance of tumors can be mediated by various cellular mechanisms including dysregulated apoptosis or ineffective drug concentration at the intracellular target sites. In this review, we highlight recent advances in experimental chemotherapy underlining the role of cellular transporters in drug resistance. Such contribution to the chemoresistant phenotype of tumor cells or tissues can be conferred both by uptake and export transporters, as demonstrated by in vivo and in vitro data. Our studies used human pancreatic carcinoma cells, cells stably transfected with human transporter cDNAs, or cells in which a specific transporter was knocked down by RNA interference. We have previously shown that 5-fluorouracil treatment affects the expression profile of relevant cellular transporters including multidrug resistance proteins (MRPs), and that MRP5 (ABCC5) influences chemoresistance of these tumor cells. Similarly, cell treatment with the nucleoside drug gemcitabine or a combination of chemotherapeutic drugs can variably influence the expression pattern and relative amount of uptake and export transporters in pancreatic carcinoma cells or select for pre-existing subpopulations. In addition, cytotoxicity studies with MRP5-overexpressing or MRP5-silenced cells demonstrate a contribution of MRP5 also to gemcitabine resistance. These data may lead to improved strategies of future chemotherapy regimens using gemcitabine and/or 5-fluorouracil. Molecular Diversity Preservation International (MDPI) 2010-12-30 /pmc/articles/PMC3756352/ /pubmed/24212609 http://dx.doi.org/10.3390/cancers3010106 Text en © 2010 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Review Hagmann, Wolfgang Faissner, Ralf Schnolzer, Martina Lohr, Matthias Jesnowski, Ralf Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma |
title | Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma |
title_full | Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma |
title_fullStr | Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma |
title_full_unstemmed | Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma |
title_short | Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma |
title_sort | membrane drug transporters and chemoresistance in human pancreatic carcinoma |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756352/ https://www.ncbi.nlm.nih.gov/pubmed/24212609 http://dx.doi.org/10.3390/cancers3010106 |
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