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

Recombinant adenovirus mediated p53 gene transfer combined with anti-cancer drugs has clinical potential for gene therapy of lung cancer. We construct ed 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 infectio n of the Ad-p53 vector into H1299 cells, RERF-LC-OK cells, or A549 cells in creased the sensitivity to all six drugs regardless of the cellular p53 sta tus, and a synergism was observed by the isobolic method in combination stu dies (D < 1). We conclude that our strategy using adenoviral mediated p53 g ene transfer to cancer cells can enhance the cytotoxic effect of anti-cance r drugs, which leading to an improvement of lung cancer chemotherapy. (C) 2 000 Elsevier Science Ireland Ltd. All rights reserved.