Glutamine inhibits platelet-activating factor-mediated pulmonary tumour metastasis.
Eur J Cancer
; 48(11): 1730-8, 2012 Jul.
Article
em En
| MEDLINE
| ID: mdl-21889331
ABSTRACT
Inflammation has been increasingly recognised as an important component of tumourigenesis. Platelet-activating factor (PAF), a potent inflammatory mediator, has the ability to enhance tumour growth and metastasis. In this study, we have investigated (i) the role of mitogen-activated protein kinases (MAPKs) and (ii) the therapeutic efficacy of the non-essential amino acid, l-glutamine (Gln), which evidences MAPKs inhibition activity in PAF-mediated B16F10 melanoma metastasis to the lungs. Mice were given intraperitoneal injection of PAF. ERK, JNK, and p38 MAPKs were activated rapidly by PAF in the lungs, and the PAF-induced metastasis of B16F10 was inhibited in a dose-dependent manner by pretreatment with either U0126 (ERK inhibitor), SP600125 (JNK inhibitor), or SB202190 (p38 inhibitor). Intraperitoneal administration of Gln after, but not before, PAF injection deactivated ERK, JNK, and p38 by dephosphorylating them. Gln inhibited PAF-induced metastasis when Gln was administered either intraperitoneally or orally. PAF induced pronounced angiogenic activity in an in vivo mouse Matrigel implantation model. MAPK inhibitors as well as Gln significantly inhibited PAF-induced angiogenesis. These data indicate that Gln exerts a beneficial effect against inflammation-associated enhanced tumour metastasis via the deactivation of MAPKs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Melanoma Experimental
/
Fator de Ativação de Plaquetas
/
Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Eur J Cancer
Ano de publicação:
2012
Tipo de documento:
Article