Evento
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma
Solernó, Luisina María
; Sobol, Natasha Tatiana
; Ferrero, Maximiliano Ruben
; Llavona, Candela; Capobianco, Carla Sabrina
; Bruzzone, Ariana
; Gottardo, María Florencia
; Garona, Juan
Tipo del evento:
Reunión
Nombre del evento:
Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología
Fecha del evento:
16/11/2022
Institución Organizadora:
Sociedad Argentina de Investigación Clínica;
Sociedad Argentina de Inmunología;
Sociedad Argentina de Fisiología;
Título de la revista:
Medicina (Buenos Aires)
Editorial:
Fundación Revista Medicina
ISSN:
0025-7680
e-ISSN:
1669-9106
Idioma:
Inglés
Clasificación temática:
Resumen
Osteosarcoma (OSA) is still associated with limited response to standard-of-care therapy and alarmingly elevated mortality rates. Our group recently reported for the first time that PPN, a repurposed β1/2-adrenergic receptor (ADRB1/2)antagonist, was capable of reducing tumor-associated angiogenesis and xenograft aggressiveness using different OSA preclinical models.The objective of this work was tocharacterize PPN ADRB2-mediated effects and mechanisms of action on OSA growth, migration and response to chemotherapy. After confirming ADRB2 expression by RT-qPCR in MG-63 and U-2OS OSA cells, pro-mitogenic effects of ADRB agonists epinephrine and norepinephrinewere associated with downstream activation of MAPK-associated signaling pathways, as evaluated by western blotting. ADRB2 knockdown by transfection with ADRB2-targeting siRNA reduced in vitro aggressiveness of OSA cells and impairedPPN cytostatic activity, confirming target specificity of the drug. As evaluated by flow cytometry, a significant arrest in the G0/G1 cell cycle phase of MG-63 and U-2OS cells was observed after 24 h treatment with PPN (50 µM), which was associated with a significant reduction in CCND1 gene expression, a key cell cycle regulator. OSA growth inhibition was not associated with apoptosis induction. β-blockade with PPN inhibited OSA cell chemotaxis, vasculogenicmimicry and capillary-like tube formationon Matrigel® coated substrates. Migration inhibition was linked toblockade of EGF-induced actin reorganization and stress fiber formation. After histological analysis, in vivo therapeutic benefits after addition of PPN (10 mg/kg i.p.) to cisplatin-based metronomic chemotherapy (2 mg/kg i.p.) correlated with reduced tumor mitotic index and increased necrosis. All results were significantat p<0.05 (t test or ANOVA, GraphPad Prism). We propose PPN as a potential cost-effectiveco-adjuvant therapy for OSA management. Further translational studies on metastatic disease are in progress.
Palabras clave:
OSTEOSARCOMA
,
BETA-BLOCKER
,
PROPRANOLOL
,
ANTITUMORAL
Archivos asociados
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Colecciones
Eventos(IBIOBA - MPSP)
Eventos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Eventos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Eventos(INIBIBB)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Eventos(SEDE CENTRAL)
Eventos de SEDE CENTRAL
Eventos de SEDE CENTRAL
Citación
Characterization of ADRB2-mediated antitumoral effects and mechanisms of action of β-blocker propranolol in osteosarcoma; Reunión Conjunta SAIC SAI & FAIC SAFIS 2022; LXVII Reunión Anual de la Sociedad Argentina de Investigación Clínica; LXX Reunión Anual de la Sociedad Argentina de Inmunología; 3er Congreso Franco Argentino de Inmunología; Reunión Anual 2022 de la Sociedad Argentina de Fisiología; Mar del Plata; Argentina; 2022; 269-269
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