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Effects of alpha-fetoprotein on the expression of TRAIL death receptor-2 and its role on resisting the cytotoxicity of TRAIL in hepatoma cells / 中华肝脏病杂志
Chinese Journal of Hepatology ; (12): 745-750, 2010.
Artigo em Chinês | WPRIM | ID: wpr-360849
ABSTRACT
<p><b>OBJECTIVE</b>To explore the mechanism of Alpha-fetoprotein (AFP) effects on hepatocellular carcinoma cells (HCC) resistances apoptosis induced by tumor necrosis factor-related apoptosis inducing-ligand (TRAIL).</p><p><b>METHODS</b>The expressed alteration of TRAIL receptor-2 (DR5) after the human hepatoma cells line Bel 7402 (AFP-producing) and HLE cells (non-AFP producing) were treated with all trans retinoic acid (ATRA) were determined by Western blot; Interaction of AFP with RAR-beta was analyzed by co-immunoprecipitation (Co-IP); Laser confocal microscopy was used to observe co-localization of AFP and RAR-beta; Short small RNA interfering (RNAi) was applied to knock down the expression of AFP in Bel 7402 cells; The full AFP gene cDNA was inserted into pcDNA3.1 vector and constructed the expressed vector of AFP (named pcDNA3.1-afp); The growth of hepatoma cells was analyzed by MTT.</p><p><b>RESULTS</b>Bel 7402 and HLE cells expressed DR5, lowed dosage of ATRA (40mumol/L) had no influence on the expression of DR5 in Bel 7402 cells, but ATRA (160mumol/L) could inhibit the expression of AFP and promote the expression of DR5 significantly; Co-IP indicated that AFP had a property for interacting with RAR-beta; The results also demonstrated AFP co-localization with RAR-beta in cytoplasm of Bel 7202 cells; The expression of DR5 was enhanced while the expression of AFP was knocked down by RNAi. pcDNA3.1-afp vector was transfected into HLE cells, the growth of HLE cells were stimulated and TRAIL cytotoxicity of HLE cells were reduced. But when the expression of AFP was knocked down the sensitivity of Bel 7402 cells to TRAIL was enhanced.</p><p><b>CONCLUSIONS</b>These data provided that AFP had a capability to interact with RAR-beta and suppressed the expression of DR5. AFP could play pivotal role on hepatoma cells resistance-induced apoptosis by TRAIL.</p>
Assuntos
Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Tretinoína / Alfa-Fetoproteínas / Apoptose / Receptores do Ácido Retinoico / Linhagem Celular Tumoral / Ligante Indutor de Apoptose Relacionado a TNF / Receptores do Ligante Indutor de Apoptose Relacionado a TNF / Metabolismo Limite: Humanos Idioma: Chinês Revista: Chinese Journal of Hepatology Ano de publicação: 2010 Tipo de documento: Artigo

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Texto completo: DisponíveL Índice: WPRIM (Pacífico Ocidental) Assunto principal: Farmacologia / Tretinoína / Alfa-Fetoproteínas / Apoptose / Receptores do Ácido Retinoico / Linhagem Celular Tumoral / Ligante Indutor de Apoptose Relacionado a TNF / Receptores do Ligante Indutor de Apoptose Relacionado a TNF / Metabolismo Limite: Humanos Idioma: Chinês Revista: Chinese Journal of Hepatology Ano de publicação: 2010 Tipo de documento: Artigo