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Acta Pharmacol Sin ; 30(10): 1436-42, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19749785

RESUMO

AIM: To determine the effect of human DNA binding protein (dbpA) on the biology of gastric cancer cells. METHODS: DbpA expression was analyzed by Western blot analysis and immunofluorescence staining in gastric cancer tissues and cell lines. A dbpA-specific small interference (si) RNA was designed and synthesized. Suppressive effect of siRNA on dbpA expression was assessed by real-time RT-PCR. Transwell migration and colony formation assays were used to assess the inhibitory effects of dbpA siRNA on cell invasion and tumorigenesis in vitro. Drug-sensitivity was evaluated using a conventional 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The expression of dbpA was upregulated in gastric cancer tissues and cell lines as compared to adjacent normal tissues or gastric epithelial cells. siRNA treatment successfully silenced dbpA expression. Silencing of dbpA increased expression of E-cadherin, decreased expression of adenomatous polyposis coli (APC), beta-catenin and cyclin D1, but had no effect on expression of NF-kappaB. Silencing of dbpA also suppressed cell invasion and colony formation of SGC7901 cells, and enhanced their chemosensitivity to 5-fluorouracil. CONCLUSION: DbpA plays an important role in the pathogenesis and development of gastric cancer, and the process involves E-cadherin, APC, beta-catenin and cyclin D1. Silencing of dbpA might be a novel therapeutic strategy for increasing chemosensitivity to 5-fluorouracil in gastric cancer.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , RNA Interferente Pequeno/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Proteína da Polipose Adenomatosa do Colo/genética , Proteína da Polipose Adenomatosa do Colo/metabolismo , Antineoplásicos/farmacologia , Proteínas Estimuladoras de Ligação a CCAAT/fisiologia , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Transformada , Linhagem Celular Tumoral , Corantes/metabolismo , Meios de Cultura Livres de Soro , Ciclina D1/genética , Ciclina D1/metabolismo , Técnica Direta de Fluorescência para Anticorpo , Fluoruracila/farmacologia , Proteínas de Choque Térmico/fisiologia , Humanos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo , Transfecção , Regulação para Cima/efeitos dos fármacos , beta Catenina/genética , beta Catenina/metabolismo
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