Document Detail


Gef gene therapy enhances the therapeutic efficacy of doxorubicin to combat growth of MCF-7 breast cancer cells.
MedLine Citation:
PMID:  19771430     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The potential use of combined therapy is under intensive study including the association between classical cytotoxic and genes encoding toxic proteins which enhanced the antitumour activity. The main aim of this work was to evaluate whether the gef gene, a suicide gene which has a demonstrated antiproliferative activity in tumour cells, improved the antitumour effect of chemotherapeutic drugs used as first-line treatment in the management of advanced breast cancer.
METHODS: MCF-7 human breast cancer cells were transfected with gef gene using pcDNA3.1-TOPO expression vector. To determine the effect of the combined therapy, MCF-7 transfected and non-transfected cells were exposed to paclitaxel, docetaxel and doxorubicin at different concentrations. The growth-inhibitory effect of gef gene and/or drugs was assessed by MTT assay. Apoptosis modulation was determined by flow cytometric analysis, DNA fragmentation and morphological analysis. Multicellular tumour spheroids (MTS) from MCF-7 cells were used to confirm effectiveness of combined therapy (gef gene and drug).
RESULTS: Our results demonstrate that combined therapy gef gene/drugs (paclitaxel, docetaxel or doxurubicin) caused a decrease in cell viability. However, only the gef-doxorubicin (10 microM) combination induced a greater enhancement in the antitumour activity in MCF-7 cells. Most importantly, this combined strategy resulted in a significant synergistic effect, thus allowing lower doses of the drug to be used to achieve the same therapeutic effect. These results were confirmed using MTS in which volume decrease with combined therapy was greater than obtained using the gene therapy or chemotherapy alone, or the sum of both therapies.
CONCLUSIONS: The cytotoxic effect of gef gene in breast cancer cells enhances the chemotherapeutic effect of doxorubicin. This therapeutic approach has the potential to overcome some of the major limitations of conventional chemotherapy, and may therefore constitute a promising strategy for future applications in breast cancer therapy.
Authors:
Jose Prados; Consolación Melguizo; Ana Rosa Rama; Rául Ortiz; Ana Segura; Houria Boulaiz; Celia Vélez; Octavio Caba; Juan Luís Ramos; Antonia Aránega
Publication Detail:
Type:  Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-22
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  66     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-14     Completed Date:  2010-05-06     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  69-78     Citation Subset:  IM    
Affiliation:
Department of Human Anatomy and Embryology, School of Medicine, Institute of Biopathology and Regenerative Medicine, University of Granada, 18071, Granada, Spain. jcprados@ugr.es
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / administration & dosage,  pharmacology
Apoptosis / drug effects
Bacterial Toxins / genetics*,  metabolism
Breast Neoplasms / drug therapy*,  genetics,  therapy*
Cell Line, Tumor
Cell Survival / drug effects
Combined Modality Therapy / methods*
Doxorubicin / administration & dosage*,  pharmacology
Drug Screening Assays, Antitumor / methods
Escherichia coli Proteins / genetics*,  metabolism
Female
Genes, Transgenic, Suicide
Genetic Therapy / methods*
Genetic Vectors
Humans
Membrane Proteins / genetics*,  metabolism
Paclitaxel / administration & dosage*,  pharmacology
Spheroids, Cellular / drug effects
Taxoids / administration & dosage,  pharmacology
Transfection / methods
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Bacterial Toxins; 0/Escherichia coli Proteins; 0/Membrane Proteins; 0/Taxoids; 128280-09-1/HokC protein, E coli; 15H5577CQD/docetaxel; 23214-92-8/Doxorubicin; 33069-62-4/Paclitaxel

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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