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.
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.
Inoue
A
A
Department of Respiratory Oncology and Molecular Medicine, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan.
Narumi
K
K
Matsubara
N
N
Sugawara
S
S
Saijo
Y
Y
Satoh
K
K
Nukiwa
T
T
D000260:Adenoviruses, Human / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression; D018014:Gene Transfer Techniques; D016158:Genes, p53 / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents