title: Gef gene therapy enhances the therapeutic efficacy of cytotoxics in colon cancer cells.
abstract: The potential use of gene therapy to improve the response of patients with advanced cancer is being intensively analyzed. We evaluated the cytotoxic impact of the gef gene, a suicide gene, which has a demonstrated antiproliferative activity in tumor cells, in colon carcinoma cells in order to improve the antitumour effect of chemotherapeutic drugs used as first line treatment in the management of advanced colon cancer. We found that the gef gene induced a marked decrease in cell viability (50% in 24h) in T-84 cells through cell death by apoptosis. Interestingly, when gef gene expression was combined with drugs of choice in the clinical treatment of colon cancer (5-fluorouracil, oxaliplatin and irinotecan), a strong synergistic effect was observed with approximately a 15-20% enhancement of the antiproliferative effect. Our data demonstrate, for the first time, that gef gene expression induces significant growth arrest in colon cancer cells and that it is able to enhance the effect of some cytotoxic drugs compared with a single therapeutic approach. These results indicate the potential therapeutic value of the gef gene in colon cancer combination therapy.
authors: Department of Health Sciences, University of Jaén, Jaén, Spain.
authors: Raúl
authors: R
authors: Ortiz
authors: Jose
authors: J
authors: Prados
authors: Consolación
authors: C
authors: Melguizo
authors: Ana R
authors: AR
authors: Rama
authors: Pablo J
authors: PJ
authors: Alvarez
authors: Fernando
authors: F
authors: Rodríguez-Serrano
authors: Octavio
authors: O
authors: Caba
authors: Houria
authors: H
authors: Boulaiz
authors: Antonia
authors: A
authors: Aranega
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D003110:Colonic Neoplasms / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D029968:Escherichia coli Proteins / Q000235:genetics*; D005472:Fluorouracil / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D000077146:Irinotecan; D008565:Membrane Proteins / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin
chemical_list: D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; C071524:HokC protein, E coli; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin