The anti-apoptotic effect of cytoplasmic alpha-fetoprotein in hepatoma cells induced by all-trans retinoic acid involves activation of the PI3K/AKT signaling pathway / 中华肝脏病杂志
Chinese Journal of Hepatology
;
(12): 837-842, 2014.
Artigo
em Chinês
| WPRIM
| ID: wpr-337095
ABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of alpha-fetoprotein (AFP) on transduction of the PI3K/ AKT signal in hepatocellular carcinoma cells and the role played by AFP in resistance to cytotoxicity of all-trans retinoic acid (ATRA).</p><p><b>METHODS</b>The effects of ATRA of human liver cancer cells was assessed using the BEL-7402 cell line with the MTT assay (to evaluate proliferation), microscopy (to evaluate morphology), flow cytometry (to evaluate apoptosis), laser confocal microscopy and coimmunoprecipitation (co-IP; to evaluate co-localization and interaction of AFP with PTEN), Western blotting (to evaluate expression of phosphorylated-protein kinase B (pAKT) and Src, and RNA interference (RNAi)-mediated knockdown of AFP. Finally, application of the PI3K-specific inhibitor Ly294002 was used to monitor the influence of AFP in transduction of the PI3K signal pathway.</p><p><b>RESULTS</b>The human hepatoma cell line BEL-7402 were resistant to ATRA cytotoxicity. PTEN and AFP co-localized in the cytoplasm, and co-IP indicated that AFP interacts with PTEN in BEL-7402 cells.RNAi knockdown of AFP expression led to reduced growth of BEL-7402 cells.BEL-7402 cells transfected with AFP-short interfering (si)RNA vectors showed enhanced sensitivity to ATRA and reduced expression of pAKT(Ser473) and Src; Ly294002 reduced the role of AFP in stimulating expression of pAKT(Ser473) and Src.</p><p><b>CONCLUSION</b>AFP can activate transduction of the PI3K/AKT signal, and expression of AFP in hepatoma cells is a pivotal event for resisting ATRA-induced apoptosis.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Fosforilação
/
Tretinoína
/
Transfecção
/
Transdução de Sinais
/
Alfa-Fetoproteínas
/
Western Blotting
/
Apoptose
/
Carcinoma Hepatocelular
/
Fosfatidilinositol 3-Quinases
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Hepatology
Ano de publicação:
2014
Tipo de documento:
Artigo
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