The role of p53 in induction of growth arrest DNA damage-inducible gene 45β in human hepatoma cells by oxaliplatin / 中华肝胆外科杂志

ABSTRACT

Objective To identify the role of p53 in the induction of growth arrest DNA damage-inducible gene 45β (GADD45β) in HCC cells by Oxaliplatin.Methods A Hep3B+p53 clone was established by transfection of the full-length p53 sequence to Hep3B.Following oxaliplatin administration,quantitative real-time PCR was employed to validate the expression changes of GADD45β.pGL3 basic luciferase plasmids including promoter fragments were synthesized in vitro and transfected into cells.The effects on promoter activity,cell growth and the cleavage of Caspase-3 were further focused on.Results Hep3B+p53 expressed p53 protein stably.The transfection of p553 enhanced the induction of GADD45β in Hep3B by Oxaliplatin.The promoter activity of fragments constructed NF-κB and E2F-1 binding sites was induced about 1.5 and 0.8 folds by transfection of p53.The colony formation and DNA syntheses were inhibited apparently in Hep3B+p53 with p53 by Oxaliplatin (30.41％ and 75.60％ by 100 μmol/L Oxaliplatin,respectively).Moreover,p53 transfection triggered cleavage of Caspase-3 more rapidly.Conclusion p53 played a role in the induction of GADD45β in Hep3B by Oxaliplatin.