14-3-3σ negatively regulates Akt and inhibits Rat1-Akt cell xenografts

AIM: The present study was designed to investigate the effect of adenovirus-mediated 14-3-3σ on Rat1-Akt cell xenografts and to explore whether the effect was mediated through negative regulation of Akt.METHODS: The effect of Ad-14-3-3σ on Rat1-Akt cells xenografts was observed in nude mice ex vivo and in vivo.Western blotting was used to detect 14-3-3σ protein,phospho-Akt(Thr 308),phospho-Akt(Ser 473),and phospho-(Ser/Thr) Akt substrate in tumor tissue after transfection of 14-3-3σ gene.RESULTS: The tumor volume was dramatically decreased and its emergence was delayed,regardless of using Ad-14-3-3σ-treated Rat1-Akt cells(ex vivo) or injected Ad-14-3-3σ in vivo,of which the effect of the continuously injected group was the best.Levels of Akt protein,phosphorylated Akt and phosphorylated Akt substrates in tumors obtained from Ad-14-3-3σ-treated mice were markedly less than those in PBS or Ad-β-gal-treated mice.CONCLUSION: 14-3-3σ suppressed Akt overexpession in cells of Rat1-Akt xenografts by negatively regulating Akt.