Effect of deoxyribozymes targeting c-Jun on solid tumor growth and angiogenesis in rodents
| Autor: | Lun-Quan Sun, Nick Di Girolamo, Eric Sumithran, Levon M. Khachigian, Guishui Zhang, Crispin R. Dass |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A Cancer Research Pathology medicine.medical_specialty Angiogenesis Proto-Oncogene Proteins c-jun Blotting Western Melanoma Experimental Angiogenesis Inhibitors Antineoplastic Agents Biology Matrix Metalloproteinase Inhibitors Transfection Cell Line Neovascularization Cornea Rats Sprague-Dawley chemistry.chemical_compound Mice Genes jun Cell Movement medicine Animals Humans Neovascularization Pathologic Cell growth Reverse Transcriptase Polymerase Chain Reaction Endothelial Cells DNA Catalytic medicine.disease Rats Vascular endothelial growth factor Endothelial stem cell Gene Expression Regulation Neoplastic Mice Inbred C57BL Vascular endothelial growth factor A Oncology chemistry Corneal neovascularization Cancer research Matrix Metalloproteinase 2 Electrophoresis Polyacrylamide Gel Female medicine.symptom Cell Division Dz13 |
| Zdroj: | Journal of the National Cancer Institute. 96(9) |
| ISSN: | 1460-2105 |
| Popis: | Background: The basic region-leucine zipper protein c-Jun has been linked to cell proliferation, transformation, and apoptosis. However, a direct role for c-Jun in angiogenesis has not been shown. Methods: We used human microvascular endothelial cells (HMEC-1) transfected with a DNAzyme targeting the c-Jun mRNA (Dz13), related oligonucleotides, or vehicle in in vitro models of microvascular endothelial cell proliferation, migration, chemoinvasion, and tubule formation, a rat model of corneal neovascularization, and a mouse model of solid tumor growth and vascular endothelial growth factor (VEGF)-induced angiogenesis. All statistical tests were two-sided. Results: Compared with mock-transfected cells, HMEC-1 cells transfected with Dz13 expressed less c-Jun protein and possessed lower DNA-binding activity. Dz13 blocked endothelial cell proliferation, migration, chemoinvasion, and tubule formation. Dz13 inhibited the endothelial cell expression and proteolytic activity of MMP-2, a c-Jun-dependent gene. Dz13 inhibited VEGF-induced neovascularization in the rat cornea compared with vehicle control (Dz13 versus vehicle: 4.0 neovessels versus 30.7 neovessels, difference = 26.7 neovessels; P = .004; area occupied by new blood vessels for Dz13 versus vehicle: 0.35 mm 2 versus 1.52 mm 2 , difference = 1.17 mm 2 ; P = .005) as well as solid melanoma growth in mice (Dz13 versus vehicle at 14 days: 108 mm 3 versus 283 mm 3 , difference = 175 mm 3 ; P = .006) with greatly reduced vascular density (Dz13 versus vehicle: 30% versus 100%, difference = 70%; P |
| Databáze: | OpenAIRE |
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