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Clin Pharmacol Ther ; 102(1): 52-61, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28139830

RESUMO

The mechanism of action of low-dose aspirin in the prevention of colorectal cancer (CRC) remains largely hypothetical. We aimed to compare the effects of low-dose aspirin (100 mg/day for 7 days) given to 40 individuals undergoing CRC screening on the extent of cyclooxygenase (COX)-1 acetylation at serine-529 (AceCOX-1), in blood platelets vs. colorectal mucosa, at 7 (group 1) and 24 h (group 2) after dosing. A significantly (P < 0.01) lower %AceCOX-1 was detected in colonic and rectal mucosa (average 64%) vs. platelets (average 75%) in both groups. This effect was associated with an average 46% (P < 0.01) and 35% (P < 0.05) reduction in prostaglandin (PG) E2 levels and phosphorylated S6 (p-S6) levels, respectively. Rectal mucosal levels of p-S6/S6 significantly (P < 0.01) correlated with PGE2 . These findings demonstrate that low-dose aspirin produces long-lasting acetylation of COX-1 and downregulation of p-S6 in human colorectal mucosa, an effect that may interfere with early colorectal carcinogenesis.


Assuntos
Aspirina , Plaquetas , Neoplasias Colorretais , Ciclo-Oxigenase 1/metabolismo , Dinoprostona/biossíntese , Mucosa Intestinal , Proteínas Quinases S6 Ribossômicas/metabolismo , Acetilação/efeitos dos fármacos , Aspirina/administração & dosagem , Aspirina/farmacocinética , Biópsia/métodos , Plaquetas/efeitos dos fármacos , Plaquetas/enzimologia , Carcinogênese/efeitos dos fármacos , Carcinogênese/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/prevenção & controle , Inibidores de Ciclo-Oxigenase/administração & dosagem , Inibidores de Ciclo-Oxigenase/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/enzimologia , Masculino , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Resultado do Tratamento
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