[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]

Zhonghua Gan Zang Bing Za Zhi. 2001 Aug;9(4):229-31.
[Article in Chinese]

Abstract

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.

MeSH terms

  • Adenoviridae / genetics
  • Apoptosis*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism
  • B7-1 Antigen / pharmacology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Division / drug effects
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Humans
  • Liver Neoplasms / pathology
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Protein p53 / pharmacology*

Substances

  • B7-1 Antigen
  • Tumor Suppressor Protein p53
  • Granulocyte-Macrophage Colony-Stimulating Factor