Effects of the dominant negative form of protein phosphatase 2A catalytic subunit α driven by alpha-fetoprotein enhancer/phosphoglycerate kinase promoter on hepatoma cell xenografts / 中华肝胆外科杂志

ABSTRACT

Objective To investigate the effects of AFP enhancer/pgk promoter driven expression of the dominant negative form of the PP2A catalytic subunit α (DN-PP2Acα) in vivo.Methods The previously constructed AFpg promoter-driven DN-PP2Acα was recombined into an adenovirus,and the expression of PP2Ac was tested using Western blot.Cell growth was tested using the MTT and flat plate clone formation assays.In vivo studies were performed in tumor xenograft models.Results AFpg promoter-driven expression of DN-PP2Acα exerted cytotoxic effects against the AFP-positive human hepatoma cell line HepG2,but did not affect AFP-negative human hepatoma cells (SKHEP-1) or normal human liver cells (L-02).Moreover,AFP enhancer/pgk promoter driven expression of DN-PP2Acα inhibited the growth of AFP-positive HepG2 tumors in nude mice bearing solid tumor xenografts,but did not affect AFP-negative SK-HEP-1 tumors.Conclusion The recombinant AFP enhancer/pgk promoter-driven DN-PP2Acα expression adenovirus presented selective cytotoxicity against AFP-positive hepatoma cells and provides a useful gene therapy strategy to selectively target hepatocellular carcinoma.