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

Akira Inoue, Koh Narumi, Nobumichi Matsubara, Shun Ichi Sugawara, Yasuo Saijo, Ken Satoh, Toshihiro Nukiwa

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)105-112
Number of pages8
JournalCancer Letters
Volume157
Issue number1
DOIs
Publication statusPublished - 2000 Aug 31

Keywords

  • Adenoviral vector
  • Anti-cancer agents
  • Lung cancer cell lines
  • Synergistic effect
  • p53

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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