Evento
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
; Rivero, Ezequiel; Rodriguez, María Sol
; Bruque, Carlos David
; Aparicio, Evangelina
; Bruzzone, Ariana
; Pérez Piñero, Cecilia; Luthy, Isabel Alicia
Tipo del evento:
Reunión
Nombre del evento:
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
Fecha del evento:
10/11/2020
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
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.
Palabras clave:
PACLITAXEL
,
SALBUTAMOL
,
BETA ADRENERGIC
,
BREAST CANCER
Archivos asociados
Licencia
Identificadores
Colecciones
Eventos(IBYME)
Eventos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Eventos de INST.DE BIOLOGIA Y MEDICINA EXPERIMENTAL (I)
Eventos(INIBIBB)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Eventos de INST.DE INVEST.BIOQUIMICAS BAHIA BLANCA (I)
Citación
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
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