Next Article in Journal
Decoding Melanoma Metastasis
Next Article in Special Issue
Dependence of Relative Expression of NTR1 and EGFR on Cell Density and Extracellular pH in Human Pancreatic Cancer Cell Lines
Previous Article in Journal
Detection of up to 65% of Precancerous Lesions of the Human Colon and Rectum by Mutation Analysis of APC, K-Ras, B-Raf and CTNNB1
Previous Article in Special Issue
Screening Technologies for Target Identification in Pancreatic Cancer
Cancers 2011, 3(1), 106-125; doi:10.3390/cancers3010106

Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma

1,* , 1
Received: 1 December 2010 / Revised: 10 December 2010 / Accepted: 24 December 2010 / Published: 30 December 2010
(This article belongs to the Special Issue Pancreatic Cancer)
View Full-Text   |   Download PDF [654 KB, uploaded 30 December 2010]   |   Browse Figures


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.
Keywords: ABC transporters; chemoresistance; pancreatic cancer; gemcitabine;
5-fluorouracil; multidrug resistance proteins; S100A4; OATPs; nucleoside transporters; RNA interference
ABC transporters; chemoresistance; pancreatic cancer; gemcitabine;
; multidrug resistance proteins; S100A4; OATPs; nucleoside transporters; RNA interference
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
MDPI and ACS Style

Hagmann, W.; Faissner, R.; Schnölzer, M.; Löhr, M.; Jesnowski, R. Membrane Drug Transporters and Chemoresistance in Human Pancreatic Carcinoma. Cancers 2011, 3, 106-125.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here


Cited By

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert