Adenovirus-mediated p53 gene transfer sensitizes hepatocellular carcinoma cells to heavy-ion radiation.
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.
Liu
Bing
B
Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, Gansu Province, PR China.
Zhang
Hong
H
Zhou
Guangming
G
Xie
Yi
Y
Hao
Jifang
J
Qiu
Rong
R
Duan
Xin
X
Zhou
Qingming
Q
D000256:Adenoviridae; D002244:Carbon / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000532:radiotherapy*; D018014:Gene Transfer Techniques; D016158:Genes, p53; D063193:Heavy Ion Radiotherapy; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D014407:Tumor Cells, Cultured
D002244:Carbon