Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hagmann, Wolfgang, Faissner, Ralf, Schnolzer, Martina, Lohr, Matthias, Jesnowski, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Molecular Diversity Preservation International (MDPI) 2010
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
_version_ 1782282080061751296
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
work_keys_str_mv AT hagmannwolfgang membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma
AT faissnerralf membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma
AT schnolzermartina membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma
AT lohrmatthias membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma
AT jesnowskiralf membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma