[Adenovirus-mediated transfer of human wild-type p53, GM-CSF, and B7-1 genes efficiently produces growth suppression and apoptosis of hepatocellular cells in vitro].
OBJECTIVE
To investigate the tumor suppressor activity of recombinant adenovirus vector expressing the human wild-type p53, GM-CSF, and B7-1 proteins (designated as BB-102) in human hepatocellular carcinoma cells (HCC) in vitro.


METHODS
The wild-type p53 BEL-7402, mutant p53 HLE, and HuH-7 HCC cell lines were infected with BB-102 at MOI of 50 in vitro. Immunohistochemical assay was used to determine p53 expressed by BB-102. Tumor suppressor activity of the expressed p53 was identified by terminal deoxynucleotidy I transferase (TdT) assay in BB-102-infected HCC cell lines.


RESULTS
p53 protein was found to express in a dose-dependent manner in BB-102-infected HCC cell lines. The proliferation of HCC cell lines were suppressed significantly at the average rates of 58.5%, 81.5%, and 71.1% for BEL-7402, HLE, and HuH-7 respectively from 4 to 10 days, accompanying inducing apoptosis in BB-102-infected HCC cell lines.


CONCLUSIONS
Besides the expression of B7-1 and GM-CSF, BB-102 is able to express p53 protein in independent manner and exerts its anti-tumor activity, which suggests that BB-102 may be useful for gene therapy against HCC in vivo.
Shi
M
M
Division of Biological Engineering, Institute of Infectious Disease, the 302nd Hospital of PLA, Beijing 100039, China.
Wang
F
F
Liu
M
M
Zhang
B
B
Qiu
Z
Z
Lei
Z
Z
Masayoshi
N
N
Gao
L
L
Wu
Z
Z
D000256:Adenoviridae / Q000235:genetics; D017209:Apoptosis; D018122:B7-1 Antigen / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D018122:B7-1 Antigen; D016159:Tumor Suppressor Protein p53; D016178:Granulocyte-Macrophage Colony-Stimulating Factor