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...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2010-12-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2072-6694/3/1/106/ |
| _version_ | 1797722158938456064 |
|---|---|
| author | Ralf Jesnowski Martina Schnölzer Matthias Löhr Wolfgang Hagmann Ralf Faissner |
| author_facet | Ralf Jesnowski Martina Schnölzer Matthias Löhr Wolfgang Hagmann Ralf Faissner |
| author_sort | Ralf Jesnowski |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T09:43:32Z |
| format | Article |
| id | doaj.art-c3940ef31f2a43e3b1fe57bed3762536 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T09:43:32Z |
| publishDate | 2010-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c3940ef31f2a43e3b1fe57bed37625362023-09-02T13:06:08ZengMDPI AGCancers2072-66942010-12-013110612510.3390/cancers3010106Membrane Drug Transporters and Chemoresistance in Human Pancreatic CarcinomaRalf JesnowskiMartina SchnölzerMatthias LöhrWolfgang HagmannRalf FaissnerPancreatic 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.http://www.mdpi.com/2072-6694/3/1/106/ABC transporterschemoresistancepancreatic cancergemcitabine5-fluorouracilmultidrug resistance proteinsS100A4OATPsnucleoside transportersRNA interference |
| spellingShingle | Ralf Jesnowski Martina Schnölzer Matthias Löhr Wolfgang Hagmann Ralf Faissner Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma Cancers ABC transporters chemoresistance pancreatic cancer gemcitabine 5-fluorouracil multidrug resistance proteins S100A4 OATPs nucleoside transporters RNA interference |
| 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 | ABC transporters chemoresistance pancreatic cancer gemcitabine 5-fluorouracil multidrug resistance proteins S100A4 OATPs nucleoside transporters RNA interference |
| url | http://www.mdpi.com/2072-6694/3/1/106/ |
| work_keys_str_mv | AT ralfjesnowski membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma AT martinaschnolzer membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma AT matthiaslohr membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma AT wolfganghagmann membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma AT ralffaissner membranedrugtransportersandchemoresistanceinhumanpancreaticcarcinoma |