Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action

Autores
Jabloñski, Martina; Rivero, Ezequiel; Rodriguez, María Sol; Bruque, Carlos David; Aparicio, Evangelina; Bruzzone, Ariana; Pérez Piñero, Cecilia; Luthy, Isabel Alicia
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Breast cancer is the leading cancer death cause of women in Ar- gentina. Beta2 adrenergic receptors have been described in several breast cancer cell lines and tumors. We have previously described (SAIC 2016, abstract 723) that the beta2 adrenergic agonist sal- butamol exerted in vitro a synergic effect with paclitaxel inhibiting cell proliferation. The aim of the present study was to assess the in vivo effect of the combination of paclitaxel and salbutamol in the triple-negative MDA-MB-231 cell line growing in nude mice. Both salbutamol (daily sc 1.2 mg/kg/day) and paclitaxel (10 mg/kg/week, ip in two injections) significantly inhibited tumor growth. Moreover, their combination inhibited very significantly this parameter. For ex- ample, day 63 (mean ± SEM in mm2): control tumors: 46,5 ± 9,70, n=8; paclitaxel: 32.4 ± 6,40, n=7, p<0.05; salbutamol 29.3 ± 7.58, n=7, p<0.05. Paclitaxel + salbutamol 9.33 ± 2.45, n=9, p<0.0001 against control, p<0.05 against each individually. The coefficient of drug interaction indicated synergism since the value obtained is < 1 (0.010, p<0.0005 in interaction by two-way ANOVA). In order to assess the mechanism of action, several in vitro exper- iments were performed. Paclitaxel diminished cell viability (trypan blue essay), while salbutamol diminished pERK/ERK ratio (using WB) and the expression of cyclin D1 gene (RT-qPCR). Moreover, both drugs enhanced apoptosis (acridine orange ethidium bromide staining assay). In preliminary results, salbutamol completely re- versed the increase of MDR1 (ABCB1) expression induced by pacli- taxel. This could account for the synergic effect of both drugs. These results suggest that the doses of chemotherapeutic drugs adminis- tered to patients in some triple negative (claudin-low) tumors could be reduced in the presence of salbutamol, diminishing their toxicity.
Fil: Jabloñski, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rivero, Ezequiel. No especifíca;
Fil: Rodriguez, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruque, Carlos David. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aparicio, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Pérez Piñero, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
Materia
PACLITAXEL
SALBUTAMOL
BETA ADRENERGIC
BREAST CANCER
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:11336/158117
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/158117
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of actionJabloñski, MartinaRivero, EzequielRodriguez, María SolBruque, Carlos DavidAparicio, EvangelinaBruzzone, ArianaPérez Piñero, CeciliaLuthy, Isabel AliciaPACLITAXELSALBUTAMOLBETA ADRENERGICBREAST CANCERhttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Breast cancer is the leading cancer death cause of women in Ar- gentina. Beta2 adrenergic receptors have been described in several breast cancer cell lines and tumors. We have previously described (SAIC 2016, abstract 723) that the beta2 adrenergic agonist sal- butamol exerted in vitro a synergic effect with paclitaxel inhibiting cell proliferation. The aim of the present study was to assess the in vivo effect of the combination of paclitaxel and salbutamol in the triple-negative MDA-MB-231 cell line growing in nude mice. Both salbutamol (daily sc 1.2 mg/kg/day) and paclitaxel (10 mg/kg/week, ip in two injections) significantly inhibited tumor growth. Moreover, their combination inhibited very significantly this parameter. For ex- ample, day 63 (mean ± SEM in mm2): control tumors: 46,5 ± 9,70, n=8; paclitaxel: 32.4 ± 6,40, n=7, p<0.05; salbutamol 29.3 ± 7.58, n=7, p<0.05. Paclitaxel + salbutamol 9.33 ± 2.45, n=9, p<0.0001 against control, p<0.05 against each individually. The coefficient of drug interaction indicated synergism since the value obtained is < 1 (0.010, p<0.0005 in interaction by two-way ANOVA). In order to assess the mechanism of action, several in vitro exper- iments were performed. Paclitaxel diminished cell viability (trypan blue essay), while salbutamol diminished pERK/ERK ratio (using WB) and the expression of cyclin D1 gene (RT-qPCR). Moreover, both drugs enhanced apoptosis (acridine orange ethidium bromide staining assay). In preliminary results, salbutamol completely re- versed the increase of MDR1 (ABCB1) expression induced by pacli- taxel. This could account for the synergic effect of both drugs. These results suggest that the doses of chemotherapeutic drugs adminis- tered to patients in some triple negative (claudin-low) tumors could be reduced in the presence of salbutamol, diminishing their toxicity.Fil: Jabloñski, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rivero, Ezequiel. No especifíca;Fil: Rodriguez, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bruque, Carlos David. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Aparicio, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; ArgentinaFil: Pérez Piñero, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaLXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de FisiologíaMar del PlataArgentinaSociedad Argentina de Investigación ClínicaSociedad Argentina de InmunologíaSociedad Argentina de FisiologíaFundación Revista Medicina2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónJournalhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/158117Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2020; 127-1270025-76801669-9106CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.medicinabuenosaires.com/indices-de-2020/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:26Zoai:ri.conicet.gov.ar:11336/158117instacron: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:34982025-09-29 10:26:26.261CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
title Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
spellingShingle Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
Jabloñski, Martina
PACLITAXEL
SALBUTAMOL
BETA ADRENERGIC
BREAST CANCER
title_short Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
title_full Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
title_fullStr Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
title_full_unstemmed Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
title_sort Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action
dc.creator.none.fl_str_mv Jabloñski, Martina
Rivero, Ezequiel
Rodriguez, María Sol
Bruque, Carlos David
Aparicio, Evangelina
Bruzzone, Ariana
Pérez Piñero, Cecilia
Luthy, Isabel Alicia
author Jabloñski, Martina
author_facet Jabloñski, Martina
Rivero, Ezequiel
Rodriguez, María Sol
Bruque, Carlos David
Aparicio, Evangelina
Bruzzone, Ariana
Pérez Piñero, Cecilia
Luthy, Isabel Alicia
author_role author
author2 Rivero, Ezequiel
Rodriguez, María Sol
Bruque, Carlos David
Aparicio, Evangelina
Bruzzone, Ariana
Pérez Piñero, Cecilia
Luthy, Isabel Alicia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv PACLITAXEL
SALBUTAMOL
BETA ADRENERGIC
BREAST CANCER
topic PACLITAXEL
SALBUTAMOL
BETA ADRENERGIC
BREAST CANCER
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Breast cancer is the leading cancer death cause of women in Ar- gentina. Beta2 adrenergic receptors have been described in several breast cancer cell lines and tumors. We have previously described (SAIC 2016, abstract 723) that the beta2 adrenergic agonist sal- butamol exerted in vitro a synergic effect with paclitaxel inhibiting cell proliferation. The aim of the present study was to assess the in vivo effect of the combination of paclitaxel and salbutamol in the triple-negative MDA-MB-231 cell line growing in nude mice. Both salbutamol (daily sc 1.2 mg/kg/day) and paclitaxel (10 mg/kg/week, ip in two injections) significantly inhibited tumor growth. Moreover, their combination inhibited very significantly this parameter. For ex- ample, day 63 (mean ± SEM in mm2): control tumors: 46,5 ± 9,70, n=8; paclitaxel: 32.4 ± 6,40, n=7, p<0.05; salbutamol 29.3 ± 7.58, n=7, p<0.05. Paclitaxel + salbutamol 9.33 ± 2.45, n=9, p<0.0001 against control, p<0.05 against each individually. The coefficient of drug interaction indicated synergism since the value obtained is < 1 (0.010, p<0.0005 in interaction by two-way ANOVA). In order to assess the mechanism of action, several in vitro exper- iments were performed. Paclitaxel diminished cell viability (trypan blue essay), while salbutamol diminished pERK/ERK ratio (using WB) and the expression of cyclin D1 gene (RT-qPCR). Moreover, both drugs enhanced apoptosis (acridine orange ethidium bromide staining assay). In preliminary results, salbutamol completely re- versed the increase of MDR1 (ABCB1) expression induced by pacli- taxel. This could account for the synergic effect of both drugs. These results suggest that the doses of chemotherapeutic drugs adminis- tered to patients in some triple negative (claudin-low) tumors could be reduced in the presence of salbutamol, diminishing their toxicity.
Fil: Jabloñski, Martina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Rivero, Ezequiel. No especifíca;
Fil: Rodriguez, María Sol. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruque, Carlos David. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Aparicio, Evangelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Bruzzone, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina
Fil: Pérez Piñero, Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
Fil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina
LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología
Mar del Plata
Argentina
Sociedad Argentina de Investigación Clínica
Sociedad Argentina de Inmunología
Sociedad Argentina de Fisiología
description Breast cancer is the leading cancer death cause of women in Ar- gentina. Beta2 adrenergic receptors have been described in several breast cancer cell lines and tumors. We have previously described (SAIC 2016, abstract 723) that the beta2 adrenergic agonist sal- butamol exerted in vitro a synergic effect with paclitaxel inhibiting cell proliferation. The aim of the present study was to assess the in vivo effect of the combination of paclitaxel and salbutamol in the triple-negative MDA-MB-231 cell line growing in nude mice. Both salbutamol (daily sc 1.2 mg/kg/day) and paclitaxel (10 mg/kg/week, ip in two injections) significantly inhibited tumor growth. Moreover, their combination inhibited very significantly this parameter. For ex- ample, day 63 (mean ± SEM in mm2): control tumors: 46,5 ± 9,70, n=8; paclitaxel: 32.4 ± 6,40, n=7, p<0.05; salbutamol 29.3 ± 7.58, n=7, p<0.05. Paclitaxel + salbutamol 9.33 ± 2.45, n=9, p<0.0001 against control, p<0.05 against each individually. The coefficient of drug interaction indicated synergism since the value obtained is < 1 (0.010, p<0.0005 in interaction by two-way ANOVA). In order to assess the mechanism of action, several in vitro exper- iments were performed. Paclitaxel diminished cell viability (trypan blue essay), while salbutamol diminished pERK/ERK ratio (using WB) and the expression of cyclin D1 gene (RT-qPCR). Moreover, both drugs enhanced apoptosis (acridine orange ethidium bromide staining assay). In preliminary results, salbutamol completely re- versed the increase of MDR1 (ABCB1) expression induced by pacli- taxel. This could account for the synergic effect of both drugs. These results suggest that the doses of chemotherapeutic drugs adminis- tered to patients in some triple negative (claudin-low) tumors could be reduced in the presence of salbutamol, diminishing their toxicity.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Journal
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/158117
Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2020; 127-127
0025-7680
1669-9106
CONICET Digital
CONICET
url http://hdl.handle.net/11336/158117
identifier_str_mv Effect of paclitaxel in combination with the beta2 adrenergic agonist salbutamol on breast cancer MDA-MB-231 cell line growing in vivo: Mechanist of action; LXV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXVIII Reunión Anual de la Sociedad Argentina de Inmunología y Reunión Anual de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2020; 127-127
0025-7680
1669-9106
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.medicinabuenosaires.com/indices-de-2020/
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/
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application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Fundación Revista Medicina
publisher.none.fl_str_mv Fundación Revista Medicina
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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