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Eur J Pharmacol ; 550(1-3): 8-14, 2006 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-17027961

RESUMO

Peripheral-type benzodiazepine receptors have been found throughout the body, and particularly, in high numbers, in neoplastic tissues such as the ovary, liver, colon, breast, prostate and brain cancer. Peripheral-type benzodiazepine receptor expression has been associated with tumor malignity, and its subcellular localization is important to define its function in tumor cells. We investigated the presence of peripheral-type benzodiazepine receptors in Ehrlich tumor cells, and the in vitro effects of peripheral-type benzodiazepine receptors ligands on tumor cell proliferation. Our results demonstrate the presence of peripheral-type benzodiazepine receptor in the nucleus of Ehrlich tumor cells (85.53+/-12.60%). They also show that diazepam and Ro5-4864 (peripheral-type benzodiazepine receptor agonists) but not clonazepam (a molecule with low affinity for the peripheral-type benzodiazepine receptor) decreased the percentage of tumor cells in G0-G1 phases and increased that of cells in S-G2-M phases. The effects of those agonists were prevented by PK11195 (a peripheral-type benzodiazepine receptor antagonist) that did not produce effects by itself. Altogether, these data suggest that the presence of peripheral-type benzodiazepine receptor within the nucleus of Ehrlich tumor cells is associated with tumor malignity and proliferation capacity.


Assuntos
Carcinoma de Ehrlich/tratamento farmacológico , Carcinoma de Ehrlich/patologia , Receptores de GABA-A/efeitos dos fármacos , Animais , Benzodiazepinonas/farmacologia , Carcinoma de Ehrlich/metabolismo , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Clonazepam/farmacologia , Citometria de Fluxo , Moduladores GABAérgicos/farmacologia , Imuno-Histoquímica , Isoquinolinas/farmacologia , Ligantes , Camundongos , Receptores de GABA-A/biossíntese
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