Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo de estudio
Tipo del documento
Intervalo de año de publicación
1.
J Theor Biol ; 572: 111562, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37348784

RESUMEN

Chemotherapeutic drugs are used to treat almost all types of cancer, but the intended response, i.e., elimination, is often incomplete, with a subset of cancer cells resisting treatment. Two critical factors play a role in chemoresistance: the p53 tumour suppressor gene and the X-linked inhibitor of apoptosis (XIAP). These proteins have been shown to act synergistically to elicit cellular responses upon DNA damage induced by chemotherapy, yet, the mechanism is poorly understood. This study introduces a mathematical model characterising the apoptosis pathway activation by p53 before and after mitochondrial outer membrane permeabilisation upon treatment with the chemotherapy Doxorubicin (Dox). "In-silico" simulations show that the p53 dynamics change dose-dependently. Under medium to high doses of Dox, p53 concentration ultimately stabilises to a high level regardless of XIAP concentrations. However, caspase-3 activation may be triggered or not depending on the XIAP induction rate, ultimately determining whether the cell will perish or resist. Consequently, the model predicts that failure to activate apoptosis in some cancer cells expressing wild-type p53 might be due to heterogeneity between cells in upregulating the XIAP protein, rather than due to the p53 protein concentration. Our model suggests that the interplay of the p53 dynamics and the XIAP induction rate is critical to determine the cancer cells' therapeutic response.


Asunto(s)
Proteína p53 Supresora de Tumor , Proteína Inhibidora de la Apoptosis Ligada a X , Proteína Inhibidora de la Apoptosis Ligada a X/genética , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis/fisiología , Muerte Celular , Doxorrubicina/farmacología , Línea Celular Tumoral
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA