Regression of established subcutaneous B16-F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway.
Novel treatment modalities, including gene therapy, are needed for patients with advanced melanoma. We evaluated whether the gef gene, a suicide gene from Escherichia coli, had a significant cytotoxic impact on melanoma in vivo. First, we used a non-viral gene delivery approach (pcDNA3.1/gef) to study the inhibition of melanoma cells (B16-F10) proliferation in vitro. Secondly, we used direct intra-tumoral injection of pcDNA3.1/gef complexed with jetPEI to deliver gef cDNA to rapidly growing murine melanomas. We demonstrated that gef gene not only has an antiproliferative effect on B16-F10 cells in vitro, but also induces an important decrease in melanoma tumor volume (77.7% in 8 days) in vivo. Interestingly, after gef gene treatment, melanoma showed apoptosis activation associated with the mitochondrial pathway, suggesting that the induction of this death mechanism may be an effective strategy for its treatment. Our in vivo results indicate that gef gene might become a suitable therapeutic strategy for patients with advanced melanoma.
Prados
Jose
J
Institute of Biopathology and Regenerative Medicine (IBIMER), Granada, Spain. jcprados@ugr.es
Melguizo
Consolación
C
Ortiz
Raúl
R
Boulaiz
Houria
H
Carrillo
Esmeralda
E
Segura
Ana
A
Rodríguez-Herva
Jose Juan
JJ
Ramos
Juan Luis
JL
Aránega
Antonia
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001427:Bacterial Toxins / Q000235:genetics / Q000627:therapeutic use*; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D029968:Escherichia coli Proteins / Q000235:genetics / Q000627:therapeutic use*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D020287:In Situ Nick-End Labeling; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology* / Q000628:therapy* / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure; D012074:Remission Induction / Q000379:methods; D014162:Transfection
D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; C071524:HokC protein, E coli; C505526:Casp8 protein, mouse; C506434:Casp9 protein, mouse; D053181:Caspase 8; D053453:Caspase 9