Antitumor activity of bax and p53 naked gene transfer in lung cancer: in vitro and in vivo analysis

Hum Gene Ther. 1998 Sep 20;9(14):2063-74. doi: 10.1089/hum.1998.9.14-2063.


In vitro and in vivo data have demonstrated that virus-mediated p53 gene transfer can induce active cell death and lung tumor regression. In contrast, the therapeutic potential of bax, another apoptosis-inducing gene, has not been described. We compared p53 and bax cytotoxic effects by transient transfection of an average of 25 +/- 5% of the H-322 and H-358 bronchioloalveolar carcinoma cell lines in vitro. Under these conditions, bax expression killed 70 to 90% of the transfected cells whereas p53 killed only 40% of them. The killing activity of both genes involved apoptosis, as shown by TUNEL staining. Surprisingly, BrdU incorporation indicated that the cells that did resist Bax toxicity were blocked in the pre-S phase of the cell cycle, a result expected for p53 only. In vivo, repeated injections of naked DNA encoding Bax or p53 inhibited the growth of 4-mm preestablished H-322 tumors in nude mice. Growth retardation only, and not inhibition, was observed in H-358, a poorly transfectable and rapidly growing tumor. These results indicate that Bax and p53 share a similar, strong antitumor activity in vivo, even if the former is a more potent inducer of apoptosis in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Survival / genetics
  • DNA / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Transfer Techniques*
  • Genes, Reporter / genetics
  • Genes, p53 / genetics*
  • Genetic Therapy / methods*
  • Immunohistochemistry
  • In Situ Nick-End Labeling
  • Liposomes / metabolism
  • Lung Neoplasms / genetics*
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / genetics
  • Neoplasms, Experimental / therapy
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Transfection / genetics
  • Tumor Cells, Cultured
  • bcl-2-Associated X Protein


  • Bax protein, mouse
  • Liposomes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • DNA