title: Synergistic antitumoral effect of combination E gene therapy and Doxorubicin in MCF-7 breast cancer cells.
abstract: The low effectiveness of conventional therapies to achieve the long-term survival of metastatic breast cancer patients calls for the development of novel options. Genes encoding cytotoxic proteins have been proposed as a new strategy to enhance the antiproliferative activity of drugs. Combined therapy using these genes and classical antitumoral drugs are under intensive study. The E gene from ϕX174 encodes a membrane protein with a toxic domain that leads to a decrease in the tumour cell growth rate. With the aim of improving the anti-tumour effect on breast cancer cells of the currently used chemotherapeutic drugs (Paclitaxel, Docetaxel and Doxorubicin), we investigated the association of E suicide gene with these drugs. The effect of the combined therapy (gene therapy and cytotoxic) was determined by treating transfected MCF-7 cells and multicellular tumour spheroids (MTS) with drugs gradient concentrations. Our results showed that E gene has a direct oncolytic effect inducing a significant decrease in the proliferation rate of the MCF-7 cells. The E gene antitumoral activity was mediated by the induction of apoptosis (mitochondrial pathway). In addition, a significant enhancement of proliferation inhibition was observed when E gene transfection was associated with cytotoxic drugs in comparison to single treatments. The use of the combined therapy E gene-Doxorubicin obtained the greatest effect on the MCF-7 growth arrest. This therapeutic association also induced a significant enhancement of the MTS volume growth inhibition. Anti-tumour activity of the chemotherapeutic drugs classically used in the treatment of breast cancer was enhanced by E gene. Our in vitro results indicate that experimental therapeutic strategy based in the combined therapy E gene and cytotoxic drugs may be of potential therapeutic value as a new strategy for patients with advanced breast cancer.
authors: Institute of Biopathology and Regenerative Medicine (IBIMER), Dept. Anatomía y Embriología, Facultad de Medicina, University of Granada, 18071 Granada, Spain.
authors: Ana R
authors: AR
authors: Rama
authors: Jose
authors: J
authors: Prados
authors: Consolacion
authors: C
authors: Melguizo
authors: Miguel
authors: M
authors: Burgos
authors: Pablo J
authors: PJ
authors: Alvarez
authors: Fernando
authors: F
authors: Rodriguez-Serrano
authors: Juan L
authors: JL
authors: Ramos
authors: A
authors: A
authors: Aranega
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018874:Spheroids, Cellular / Q000187:drug effects; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics*
chemical_list: D000903:Antibiotics, Antineoplastic; C029555:E protein, bacteriophage X174; D014764:Viral Proteins; D004317:Doxorubicin