Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell car...

Autores
Theile, Dirk; Gal, Zoltan; Warta, Rolf; Rigalli, Juan Pablo; Lahrmann, Bernd; Grabe, Niels; Herold Mende, Christel; Dyckhoff, Gerhard; Weiss, Johanna
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Drug-induced multidrug resistance (MDR) has been linked to overexpression of drug transporting proteins in head and neck squamous cell carcinoma (HNSCC) in vitro. The aim of this work was to reassess these findings in a murine xenograft model. NOD-SCID mice xenotransplanted with 106 HNO97 cells were treated for four consecutive weeks with weekly paclitaxel, biweekly cisplatin (both intraperitoneal), or 5-fluorouracil (5-FU, administered by osmotic pump). Tumor volume and body weight were weekly documented. Expression of drug transporters and Ki-67 marker were examined using quantitative real-time polymerase chain reaction and/or immunohistochemistry. Both paclitaxel and cisplatin significantly reduced tumor volumes after 2–3 weeks. 5-FU-treated animals had significantly lower body weights after 2 or 4 weeks of chemotherapy. None of the drugs affected expression of drug transporters at the mRNA level. However, P-glycoprotein (Pgp) protein expression was increased by paclitaxel (P < 0.01). Ki-67 expression did not change during treatment irrespective of the drug applied. Paclitaxel and cisplatin are effectively tumor volume reducing drugs in a murine xenograft model of HNSCC. Paclitaxel enhanced Pgp expression at the protein level, but not at the mRNA level suggesting transcriptional induction to be of minor relevance. In contrast, posttranscriptional mechanisms or Darwinian selection of intrinsically drug transporter overexpressing MDR cells might lead to iatrogenic chemotherapy resistance in HNSCC.
Fil: Theile, Dirk. Universität Heidelberg; Alemania
Fil: Gal, Zoltan. Universität Heidelberg; Alemania
Fil: Warta, Rolf. Universität Heidelberg; Alemania
Fil: Rigalli, Juan Pablo. Universität Heidelberg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lahrmann, Bernd. Universität Heidelberg; Alemania
Fil: Grabe, Niels. Universität Heidelberg; Alemania
Fil: Herold Mende, Christel. Universität Heidelberg; Alemania
Fil: Dyckhoff, Gerhard. Universität Heidelberg; Alemania
Fil: Weiss, Johanna. Universität Heidelberg; Alemania
Materia
Hnscc
Chemotherapy
Chemoresistance
Fluorouracil
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/15411
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/15411
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinomaTheile, DirkGal, ZoltanWarta, RolfRigalli, Juan PabloLahrmann, BerndGrabe, NielsHerold Mende, ChristelDyckhoff, GerhardWeiss, JohannaHnsccChemotherapyChemoresistanceFluorouracilhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Drug-induced multidrug resistance (MDR) has been linked to overexpression of drug transporting proteins in head and neck squamous cell carcinoma (HNSCC) in vitro. The aim of this work was to reassess these findings in a murine xenograft model. NOD-SCID mice xenotransplanted with 106 HNO97 cells were treated for four consecutive weeks with weekly paclitaxel, biweekly cisplatin (both intraperitoneal), or 5-fluorouracil (5-FU, administered by osmotic pump). Tumor volume and body weight were weekly documented. Expression of drug transporters and Ki-67 marker were examined using quantitative real-time polymerase chain reaction and/or immunohistochemistry. Both paclitaxel and cisplatin significantly reduced tumor volumes after 2–3 weeks. 5-FU-treated animals had significantly lower body weights after 2 or 4 weeks of chemotherapy. None of the drugs affected expression of drug transporters at the mRNA level. However, P-glycoprotein (Pgp) protein expression was increased by paclitaxel (P < 0.01). Ki-67 expression did not change during treatment irrespective of the drug applied. Paclitaxel and cisplatin are effectively tumor volume reducing drugs in a murine xenograft model of HNSCC. Paclitaxel enhanced Pgp expression at the protein level, but not at the mRNA level suggesting transcriptional induction to be of minor relevance. In contrast, posttranscriptional mechanisms or Darwinian selection of intrinsically drug transporter overexpressing MDR cells might lead to iatrogenic chemotherapy resistance in HNSCC.Fil: Theile, Dirk. Universität Heidelberg; AlemaniaFil: Gal, Zoltan. Universität Heidelberg; AlemaniaFil: Warta, Rolf. Universität Heidelberg; AlemaniaFil: Rigalli, Juan Pablo. Universität Heidelberg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lahrmann, Bernd. Universität Heidelberg; AlemaniaFil: Grabe, Niels. Universität Heidelberg; AlemaniaFil: Herold Mende, Christel. Universität Heidelberg; AlemaniaFil: Dyckhoff, Gerhard. Universität Heidelberg; AlemaniaFil: Weiss, Johanna. Universität Heidelberg; AlemaniaLandes Bioscience2014-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/15411Theile, Dirk; Gal, Zoltan; Warta, Rolf; Rigalli, Juan Pablo; Lahrmann, Bernd; et al.; Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma; Landes Bioscience; Cancer Biology & Therapy; 15; 4; 4-2014; 436-4421538-4047enginfo:eu-repo/semantics/altIdentifier/doi/10.4161/cbt.27632info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.4161/cbt.27632info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:16:24Zoai:ri.conicet.gov.ar:11336/15411instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:16:24.358CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
title Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
spellingShingle Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
Theile, Dirk
Hnscc
Chemotherapy
Chemoresistance
Fluorouracil
title_short Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
title_full Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
title_fullStr Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
title_full_unstemmed Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
title_sort Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma
dc.creator.none.fl_str_mv Theile, Dirk
Gal, Zoltan
Warta, Rolf
Rigalli, Juan Pablo
Lahrmann, Bernd
Grabe, Niels
Herold Mende, Christel
Dyckhoff, Gerhard
Weiss, Johanna
author Theile, Dirk
author_facet Theile, Dirk
Gal, Zoltan
Warta, Rolf
Rigalli, Juan Pablo
Lahrmann, Bernd
Grabe, Niels
Herold Mende, Christel
Dyckhoff, Gerhard
Weiss, Johanna
author_role author
author2 Gal, Zoltan
Warta, Rolf
Rigalli, Juan Pablo
Lahrmann, Bernd
Grabe, Niels
Herold Mende, Christel
Dyckhoff, Gerhard
Weiss, Johanna
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hnscc
Chemotherapy
Chemoresistance
Fluorouracil
topic Hnscc
Chemotherapy
Chemoresistance
Fluorouracil
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Drug-induced multidrug resistance (MDR) has been linked to overexpression of drug transporting proteins in head and neck squamous cell carcinoma (HNSCC) in vitro. The aim of this work was to reassess these findings in a murine xenograft model. NOD-SCID mice xenotransplanted with 106 HNO97 cells were treated for four consecutive weeks with weekly paclitaxel, biweekly cisplatin (both intraperitoneal), or 5-fluorouracil (5-FU, administered by osmotic pump). Tumor volume and body weight were weekly documented. Expression of drug transporters and Ki-67 marker were examined using quantitative real-time polymerase chain reaction and/or immunohistochemistry. Both paclitaxel and cisplatin significantly reduced tumor volumes after 2–3 weeks. 5-FU-treated animals had significantly lower body weights after 2 or 4 weeks of chemotherapy. None of the drugs affected expression of drug transporters at the mRNA level. However, P-glycoprotein (Pgp) protein expression was increased by paclitaxel (P < 0.01). Ki-67 expression did not change during treatment irrespective of the drug applied. Paclitaxel and cisplatin are effectively tumor volume reducing drugs in a murine xenograft model of HNSCC. Paclitaxel enhanced Pgp expression at the protein level, but not at the mRNA level suggesting transcriptional induction to be of minor relevance. In contrast, posttranscriptional mechanisms or Darwinian selection of intrinsically drug transporter overexpressing MDR cells might lead to iatrogenic chemotherapy resistance in HNSCC.
Fil: Theile, Dirk. Universität Heidelberg; Alemania
Fil: Gal, Zoltan. Universität Heidelberg; Alemania
Fil: Warta, Rolf. Universität Heidelberg; Alemania
Fil: Rigalli, Juan Pablo. Universität Heidelberg; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lahrmann, Bernd. Universität Heidelberg; Alemania
Fil: Grabe, Niels. Universität Heidelberg; Alemania
Fil: Herold Mende, Christel. Universität Heidelberg; Alemania
Fil: Dyckhoff, Gerhard. Universität Heidelberg; Alemania
Fil: Weiss, Johanna. Universität Heidelberg; Alemania
description Drug-induced multidrug resistance (MDR) has been linked to overexpression of drug transporting proteins in head and neck squamous cell carcinoma (HNSCC) in vitro. The aim of this work was to reassess these findings in a murine xenograft model. NOD-SCID mice xenotransplanted with 106 HNO97 cells were treated for four consecutive weeks with weekly paclitaxel, biweekly cisplatin (both intraperitoneal), or 5-fluorouracil (5-FU, administered by osmotic pump). Tumor volume and body weight were weekly documented. Expression of drug transporters and Ki-67 marker were examined using quantitative real-time polymerase chain reaction and/or immunohistochemistry. Both paclitaxel and cisplatin significantly reduced tumor volumes after 2–3 weeks. 5-FU-treated animals had significantly lower body weights after 2 or 4 weeks of chemotherapy. None of the drugs affected expression of drug transporters at the mRNA level. However, P-glycoprotein (Pgp) protein expression was increased by paclitaxel (P < 0.01). Ki-67 expression did not change during treatment irrespective of the drug applied. Paclitaxel and cisplatin are effectively tumor volume reducing drugs in a murine xenograft model of HNSCC. Paclitaxel enhanced Pgp expression at the protein level, but not at the mRNA level suggesting transcriptional induction to be of minor relevance. In contrast, posttranscriptional mechanisms or Darwinian selection of intrinsically drug transporter overexpressing MDR cells might lead to iatrogenic chemotherapy resistance in HNSCC.
publishDate 2014
dc.date.none.fl_str_mv 2014-04
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/15411
Theile, Dirk; Gal, Zoltan; Warta, Rolf; Rigalli, Juan Pablo; Lahrmann, Bernd; et al.; Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma; Landes Bioscience; Cancer Biology & Therapy; 15; 4; 4-2014; 436-442
1538-4047
url http://hdl.handle.net/11336/15411
identifier_str_mv Theile, Dirk; Gal, Zoltan; Warta, Rolf; Rigalli, Juan Pablo; Lahrmann, Bernd; et al.; Antiproliferative efficacies but minor drug transporter inducing effects of paclitaxel, cisplatin, or 5-fluorouracil in a murine xenograft model for head and neck squamous cell carcinoma; Landes Bioscience; Cancer Biology & Therapy; 15; 4; 4-2014; 436-442
1538-4047
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.4161/cbt.27632
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/abs/10.4161/cbt.27632
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Landes Bioscience
publisher.none.fl_str_mv Landes Bioscience
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.993085

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