Administration of wild-type p53 adenoviral vector synergistically enhances the cytotoxicity of anti-cancer drugs in human lung cancer cells irrespective of the status of p53 gene

Cancer Lett. 2000 Aug 31;157(1):105-12. doi: 10.1016/s0304-3835(00)00480-8.


Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs has clinical potential for gene therapy of lung cancer. We constructed a recombinant adenoviral vector expressing wild-type p53 cDNA (Ad-p53), and assessed the efficacy of a combined treatment with Ad-p53 and six anti-cancer drugs (cisplatin, 5-fluorouracil, doxorubicin, docetaxel, irinotecan, and etoposide) for human lung cancer cell lines, H1299 (with deleted p53), RERF-LC-OK (with mutant p53), and A549 (with wild-type p53). The infection of the Ad-p53 vector into H1299 cells, RERF-LC-OK cells, or A549 cells increased the sensitivity to all six drugs regardless of the cellular p53 status, and a synergism was observed by the isobolic method in combination studies (D<1). We conclude that our strategy using adenoviral mediated p53 gene transfer to cancer cells can enhance the cytotoxic effect of anti-cancer drugs, which leading to an improvement of lung cancer chemotherapy.

MeSH terms

  • Adenoviruses, Human / genetics
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Division / drug effects
  • Cell Division / genetics
  • Combined Modality Therapy
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • G1 Phase / drug effects
  • G1 Phase / genetics
  • Gene Expression
  • Gene Transfer Techniques
  • Genes, p53 / genetics*
  • Genetic Vectors / genetics
  • Genetic Vectors / pharmacology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Tumor Cells, Cultured


  • Antineoplastic Agents