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The Beta2-adrenergic agonist salbutamol synergizes with paclitaxel on cell proliferation and tumor growth in triple negative breast cancer models.
Jabloñski, Martina; Rodríguez, María Sol; Rivero, Ezequiel Mariano; Bruque, Carlos David; Vanzulli, Silvia; Bruzzone, Ariana; Pérez Piñero, Cecilia; Lüthy, Isabel Alicia.
Afiliação
  • Jabloñski M; Instituto de Biología y Medicina Experimental (IBYME-CONICET), Obligado 2490, Ciudad Autónoma de Buenos Aires, Argentina.
  • Rodríguez MS; Instituto de Biología y Medicina Experimental (IBYME-CONICET), Obligado 2490, Ciudad Autónoma de Buenos Aires, Argentina.
  • Rivero EM; Instituto de Biología y Medicina Experimental (IBYME-CONICET), Obligado 2490, Ciudad Autónoma de Buenos Aires, Argentina.
  • Bruque CD; Centre for Genomic Regulation, Barcelona, Spain.
  • Vanzulli S; Unidad de Conocimiento Traslacional Hospitalaria Patagónica, Hospital de Alta Complejidad SAMIC - El Calafate, El Calafate, Argentina.
  • Bruzzone A; Independent Pathologist, Buenos Aires, Argentina.
  • Pérez Piñero C; Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB-CONICET), Bahía Blanca, Argentina.
  • Lüthy IA; Instituto de Biología y Medicina Experimental (IBYME-CONICET), Obligado 2490, Ciudad Autónoma de Buenos Aires, Argentina. cperez.pinero@gmail.com.
Cancer Chemother Pharmacol ; 92(6): 485-499, 2023 12.
Article em En | MEDLINE | ID: mdl-37725114
ABSTRACT

PURPOSE:

Globally breast cancer accounts for 24.5% in incidence and 15.5% in cancer deaths in women. The triple-negative subtype lacks any specific therapy and is treated with chemotherapy, resulting in significant side-effects. We aimed to investigate if the dose of chemotherapeutic drugs could be diminished by co-administering it with the ß2-agonist salbutamol.

METHODS:

Cell proliferation was measured by thymidine incorporation; gene expression, by real-time PCR and protein phosphorylation by WB. Apoptosis was assessed by acridine orange / ethidium bromide and TUNEL tests. Public patient databases were consulted. Cells were inoculated to nude mice and their growth assessed.

RESULTS:

The ß2-agonist salbutamol synergizes in MDA-MB-231 cells in vitro with paclitaxel and doxorubicin on cell proliferation through ADRB2 receptors, while the ß-blocker propranolol does not. The expression of this receptor was assessed in patient databases and other cell lines. Triple negative samples had the lowest expression. Salbutamol and paclitaxel decreased MDA-MB-231 cell proliferation while their combination further inhibited it. The pathways involved were analyzed. When these cells were inoculated to nude mice, paclitaxel and salbutamol inhibited tumor growth. The combined effect was significantly greater. Paclitaxel increased the expression of MDR1 while salbutamol partially reversed this increase.

CONCLUSION:

While the effect of salbutamol was mainly on cell proliferation, suboptimal concentrations of paclitaxel provoked a very important enhancement of apoptosis. The latter enhanced transporter proteins as MDR1, whose expression were diminished by salbutamol. The expression of ADRB2 should be assessed in the biopsy or tumor to eventually select patients that could benefit from salbutamol repurposing.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Neoplasias de Mama Triplo Negativas Limite: Animals / Female / Humans Idioma: En Revista: Cancer Chemother Pharmacol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Neoplasias de Mama Triplo Negativas Limite: Animals / Female / Humans Idioma: En Revista: Cancer Chemother Pharmacol Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Argentina
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