RÉSUMÉ
Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA- induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.
Sujet(s)
Femelle , Humains , Butadiènes/pharmacologie , Lignée cellulaire tumorale , Mouvement cellulaire/effets des médicaments et des substances chimiques , Cyclooxygenase 2/biosynthèse , Extracellular Signal-Regulated MAP Kinases/antagonistes et inhibiteurs , Flavonoïdes/pharmacologie , Sous-unités alpha Gi-Go des protéines G/antagonistes et inhibiteurs , Lysophospholipides/pharmacologie , Nitriles/pharmacologie , Tumeurs de l'ovaire/métabolisme , Toxine pertussique/pharmacologie , Protein-tyrosine kinases/antagonistes et inhibiteurs , Protéines proto-oncogènes/antagonistes et inhibiteurs , Pyrimidines/pharmacologie , Récepteurs ErbB/antagonistes et inhibiteurs , Récepteurs à l'acide phosphatidique/métabolisme , Récepteur prostaglandine E/métabolisme , Transduction du signal , Activation de la transcription , Tyrphostines/pharmacologieRÉSUMÉ
(...) Com o objetivo de abordar tais vias parasito, estudamos bioquimicamente e citoquimicamente a atividade fosfatase ácida. Parasitos tratados com os três inibidores po 1h e 24h apresetaram atividade fosfatase ácida secretada significativametne dimunuída. com a finalidade de estudar as vias de sinalização do parasito na interação com a célula hospedeira, promastigotas pré-tratados com os antagonistas foram incubados com macrófagos peritoneais. Observamos que estaurosporina 1μM inibiu, de forma significativa, a internalização e a sobrevivência intracelular dos parasitos. Nossos dados sugerem que inibidores de proteína cinases podem exercer efeitos na morfologia, infectividade e proliferação de Leishmania, bloqueando o ciclo celular desses parasitos.
Sujet(s)
Phosphorylation , Techniques in vitro , Antienzymes/métabolisme , Leishmania mexicana/enzymologie , Protéine kinase C/physiologie , Technique de Western , Électrophorèse sur gel de polyacrylamide , Staurosporine/pharmacologie , Génistéine/pharmacologie , Microscopie électronique à transmission , Phosphorylation , Interactions hôte-parasite , Tyrphostines/pharmacologieRÉSUMÉ
1) A beta agonist stimulated Na+ transport and decreased the intracellular Cl concentration ([Cl]c) associated with cell shrinkage via an increase in cytosolic cAMP level by activating adenylate cyclase in rat fetal distal lung epithelial (FDLE) cells. 2) Lowering [Cl-]c activated a 28-pS nonselective cation (NSC) channel by elongating the open time of the channel. 3) cAMP signals were converted to a protein tyrosine kinase (PTK)-mediated signal. 4) The PTK-mediated signal was involved in the cAMP-stimulated Na+ transport in rat FDLE cells.