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dc.contributor.author
Rigalli, Juan Pablo
dc.contributor.author
Reuter, Tasmin
dc.contributor.author
Herold Mende, Christel
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Dyckhoff, Gerhard
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Haefeli, Walter Emil
dc.contributor.author
Weiss, Johanna
dc.contributor.author
Theile, Dirk
dc.date.available
2016-06-08T16:20:55Z
dc.date.issued
2013-05
dc.identifier.citation
Rigalli, Juan Pablo; Reuter, Tasmin ; Herold Mende, Christel; Dyckhoff, Gerhard; Haefeli, Walter Emil; et al.; Minor role of pregnane-x-receptor for acquired multidrug resistance in head and neck squamous cell carcinoma in vitro; Springer; Cancer Chemotherapy And Pharmacology; 71; 5; 5-2013; 1335-1343
dc.identifier.issn
0344-5704
dc.identifier.uri
http://hdl.handle.net/11336/6115
dc.description.abstract
Purpose: Acquired multidrug resistance (MDR) has been linked to overexpression of drug-metabolising and transporting proteins mediated by pregnane-x-receptor (PXR). The aim of this work was to establish the relevance of PXR for MDR in head and neck squamous cell carcinoma (HNSCC).
Methods: Using eight HNSCC cell lines, we determined the efficacy of paclitaxel, cisplatin and 5-fluorouracil (5-FU) via proliferation assays and determined the expression and activity of PXR through quantitative real-time polymerase chain reaction, western blotting and luciferase-based reporter gene assay. PXR knockdown approaches using shRNA-encoding vectors were applied to estimate the role of PXR for native MDR.
Results: Drug resistance ranged between 5.2 and 620 nM for paclitaxel, varied between 4.5 and 58 μM for cisplatin, and varied between 1.1 and 5,467 μM for 5-FU. Lack of PXR mRNA expression was mostly accompanied by the absence of mRNA expression of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp, ABCB1) expression. Neither mRNA nor protein expression of PXR correlated with drug resistance. However, PXR activity tended to correlate with IC50 values of paclitaxel (p = 0.08). Knockdown of PXR in one of the cell lines had a slight but not significant impact on paclitaxel efficacy compared to scrambled sequence control. Surprisingly, only in two cell lines, PXR activity was increased by the well-known inductor rifampicin.
Conclusion: This study suggests a malfunctioning of PXR and thus a minor relevance for iatrogenic chemotherapy resistance in HNSCC.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Springer
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Hnscc
dc.subject
Chemotherapy
dc.subject
Pxr
dc.subject
Mdr
dc.subject.classification
Farmacología y Farmacia
dc.subject.classification
Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Minor role of pregnane-x-receptor for acquired multidrug resistance in head and neck squamous cell carcinoma in vitro
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-06-01T13:33:12Z
dc.journal.volume
71
dc.journal.number
5
dc.journal.pagination
1335-1343
dc.journal.pais
Alemania
dc.journal.ciudad
Berlin
dc.description.fil
Fil: Rigalli, Juan Pablo. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil
Fil: Reuter, Tasmin . University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemania
dc.description.fil
Fil: Herold Mende, Christel. University of Heidelberg; Alemania
dc.description.fil
Fil: Dyckhoff, Gerhard. University of Heidelberg; Alemania
dc.description.fil
Fil: Haefeli, Walter Emil. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemania
dc.description.fil
Fil: Weiss, Johanna. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemania
dc.description.fil
Fil: Theile, Dirk. University of Heidelberg. Department of Clinical Pharmacology and Pharmacoepidemiology; Alemania
dc.journal.title
Cancer Chemotherapy And Pharmacology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/article/10.1007%2Fs00280-013-2133-x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00280-013-2133-x
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00280-013-2133-x
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