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Pancreas ; 43(1): 15-21, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24326363

RESUMO

OBJECTIVES: Pancreatic cancer remains a lethal disease. In this study, we investigated the efficacy of a combination of gastrin-releasing peptide receptor antagonist RC-3095 and gemcitabine on pancreatic cancer CFPAC-1. METHODS: The antiproliferation effects of RC-3095, gemcitabine, or the combination on pancreatic cancer were monitored in vitro. Nude mice bearing xenografts of CFPAC-1 cell received injections of the vehicle (control), RC-3095 (20 µg, subcutaneously, daily), gemcitabine (15 mg/kg, intraperitoneally, every 3 days), or the combination of RC-3095 and gemcitabine for 4 weeks. The histological changes and protein expression were tested using immunohistochemistry and Western blotting. RESULTS: Treatment with the combination in culture exhibited a powerful inhibition effect on CFPAC-1 cell proliferation. In xenograft mice model, RC-3095 or gemcitabine significantly reduced the volume and weight of tumors after 4 weeks of treatment, as compared with controls. The combination more potently inhibited the tumor growth than either agent used individually. Immunohistochemistry and Western blotting showed gastrin-releasing peptide receptor/bombesin receptor subtype-3 positive cells and protein expression in tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in combination. CONCLUSIONS: Our data suggested that the combination could be considered for the possible new approaches for treatment of pancreatic cancers.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bombesina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Neoplasias Pancreáticas/tratamento farmacológico , Fragmentos de Peptídeos/farmacologia , Receptores da Bombesina/antagonistas & inibidores , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacologia , Western Blotting , Bombesina/administração & dosagem , Bombesina/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Desoxicitidina/administração & dosagem , Desoxicitidina/farmacologia , Sinergismo Farmacológico , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fragmentos de Peptídeos/administração & dosagem , Receptores da Bombesina/metabolismo , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
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