Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids

Autores
Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
We evaluated the effect of hIFNΒ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNΒ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNΒ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy- sensitive EW7 monolayers, the combination of hIFNΒ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNΒ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy- resistant EW7 spheroids or M8 cells, the combination of hIFNΒ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNΒ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNΒ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNΒ-expressing cells killed more than 60 or 80% of cell population, respectively.
Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Gil Cardeza, Maria Lourdes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
Materia
CHEMOTHERAPY
EWING SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
SPHEROIDS
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:11336/161977
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/161977
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroidsVillaverde, Marcela SolangeGil Cardeza, Maria LourdesGlikin, Gerardo ClaudioFinocchiaro, Liliana Maria ElenaCHEMOTHERAPYEWING SARCOMAINTERFERON-BLIPOFECTIONMELANOMASPHEROIDShttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3We evaluated the effect of hIFNΒ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNΒ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNΒ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy- sensitive EW7 monolayers, the combination of hIFNΒ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNΒ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy- resistant EW7 spheroids or M8 cells, the combination of hIFNΒ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNΒ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNΒ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNΒ-expressing cells killed more than 60 or 80% of cell population, respectively.Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Gil Cardeza, Maria Lourdes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaNature Publishing Group2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/161977Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids; Nature Publishing Group; Cancer Gene Therapy; 19; 7; 5-2012; 508-5160929-1903CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cgt201227info:eu-repo/semantics/altIdentifier/doi/10.1038/cgt.2012.27info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:15Zoai:ri.conicet.gov.ar:11336/161977instacron: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:34982025-09-03 09:46:16.013CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
title Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
spellingShingle Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
Villaverde, Marcela Solange
CHEMOTHERAPY
EWING SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
SPHEROIDS
title_short Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
title_full Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
title_fullStr Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
title_full_unstemmed Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
title_sort Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids
dc.creator.none.fl_str_mv Villaverde, Marcela Solange
Gil Cardeza, Maria Lourdes
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author Villaverde, Marcela Solange
author_facet Villaverde, Marcela Solange
Gil Cardeza, Maria Lourdes
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author_role author
author2 Gil Cardeza, Maria Lourdes
Glikin, Gerardo Claudio
Finocchiaro, Liliana Maria Elena
author2_role author
author
author
dc.subject.none.fl_str_mv CHEMOTHERAPY
EWING SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
SPHEROIDS
topic CHEMOTHERAPY
EWING SARCOMA
INTERFERON-B
LIPOFECTION
MELANOMA
SPHEROIDS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv We evaluated the effect of hIFNΒ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNΒ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNΒ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy- sensitive EW7 monolayers, the combination of hIFNΒ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNΒ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy- resistant EW7 spheroids or M8 cells, the combination of hIFNΒ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNΒ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNΒ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNΒ-expressing cells killed more than 60 or 80% of cell population, respectively.
Fil: Villaverde, Marcela Solange. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Gil Cardeza, Maria Lourdes. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Glikin, Gerardo Claudio. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Finocchiaro, Liliana Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentina
description We evaluated the effect of hIFNΒ gene transfer alone or in combination with different antineoplastic drugs commonly used in cancer treatment. Five human tumor-derived cell lines were cultured as monolayers and spheroids. Four cell lines (Ewing sarcomas EW7 and COH, melanoma M8 and mammary carcinoma MCF-7) were sensitive to hIFNΒ gene lipofection. Although this effect appeared in both culture configurations, spheroids showed a relative multicellular resistance (insensitive colon carcinoma HT-29 excluded). EW7 and M8 hIFNΒ-expressing cells were exposed to different concentrations of bleomycin, bortezomib, carboplatin, doxorubicin, etoposide, methotrexate, paclitaxel and vincristine in both configuration models. In chemotherapy- sensitive EW7 monolayers, the combination of hIFNΒ gene and antineoplastic drugs displayed only additive or counteractive (methotrexate) effects, suggesting that cytotoxic mechanisms triggered by hIFNΒ gene lipofection could be saturating the signaling pathways. Conversely, in chemotherapy- resistant EW7 spheroids or M8 cells, the combination of hIFNΒ with drugs that mainly operate at the genotoxic level (doxorubicin, methotrexate and paclitaxel) presented only additive effects. However, drugs that also increase pro-oxidant species can complement the antitumor efficacy of the hIFNΒ gene and clearly caused potentiated effects (bleomycin, bortezomib, carboplatin, etoposide and vincristine). The great bystander effect induced by hIFNΒ gene lipofection could be among the main causes of its effectiveness, because only 1 or 2% of EW7 or M8 hIFNΒ-expressing cells killed more than 60 or 80% of cell population, respectively.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
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/11336/161977
Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids; Nature Publishing Group; Cancer Gene Therapy; 19; 7; 5-2012; 508-516
0929-1903
CONICET Digital
CONICET
url http://hdl.handle.net/11336/161977
identifier_str_mv Villaverde, Marcela Solange; Gil Cardeza, Maria Lourdes; Glikin, Gerardo Claudio; Finocchiaro, Liliana Maria Elena; Interferon-B lipofection I: Increased efficacy of chemotherapeutic drugs on human tumor cells derived monolayers and spheroids; Nature Publishing Group; Cancer Gene Therapy; 19; 7; 5-2012; 508-516
0929-1903
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/cgt201227
info:eu-repo/semantics/altIdentifier/doi/10.1038/cgt.2012.27
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
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 13.13397

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