Background: The purpose of this study was to investigate whether adenovirus-mediated p53 transfer could sensitize hepatocellular carcinoma to heavy-ion irradiation.
Methods: HepG2 cells were preexposed to a (12)C(6+) beam, and then infected with replication-deficient adenovirus recombinant vectors containing human wild-type p53 (AdCMV-p53) ((12)C(6+) irradiation + AdCMV-p53 infection). The survival fraction was determined by clonogenic assay. The cell cycle, cell apoptosis, and p53 expression were monitored by flow cytometric analysis.
Results: p53 expression in (12)C(6+) irradiation + AdCMV-p53 infection groups was markedly higher than that in (12)C(6+) irradiation only groups (P < 0.05), suggesting that the preexposure to the (12)C(6+) beam promoted the expression of exogenous p53 in HepG2 cells infected with AdCMV-p53 only. The G(1)-phase arrest and cell apoptosis in the (12)C(6+) irradiation + AdCMV-p53 infection groups were significantly more than those in the (12)C(6+) irradiated groups (P < 0.05). The survival fractions of the (12)C(6+) irradiation + AdCMV-p53 infection groups decreased by 30%-49% compared with those of the (12)C(6+) beam-irradiated only groups (P < 0.05).
Conclusions: Adenovirus-mediated p53 gene transfer can promote G(1)-phase arrest and cell apoptosis, thus sensitizing hepatocellular carcinoma cells to heavy-ion irradiation.