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Kamlah, F; Eul, BG; Li, S; Lang, N; Marsh, LM; Seeger, W; Grimminger, F; Rose, F; Hänze, J.
Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model.
Cancer Gene Ther. 2009; 16(3): 195-205. [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Marsh Leigh
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Abstract:
Different routes for the in vivo administration of synthetic siRNA complexes targeting lung tumors were compared, and siRNA complexes were administered for the inhibition of hypoxia-inducible factor (HIF-1alpha and HIF-2alpha). Intravenous jugular vein injection of siRNA proved to be the most effective means of targeting lung tumor tissue in the Lewis lung carcinoma (LLC1) model. In comparison, intraperitoneal injection of siRNA was not suitable for targeting of lung tumor and intratracheal administration of siRNA exclusively targeted macrophages. Inhibition of HIF-1alpha and HIF-2alpha by siRNA injected intravenously was validated by immunohistofluorescent analysis for glucose-transporter-1 (GLUT-1), a well-established HIF target protein. The GLUT-1 signal was strongly attenuated in the lung tumors of mice treated with siRNA-targeting HIF-1alpha and HIF-2alpha, compared with mice treated with control siRNA. Interestingly, injection of siRNA directed against HIF-1alpha and HIF-2alpha into LLC1 lung tumor-bearing mice resulted in prolonged survival. Immunohistological analysis of the lung tumors from mice treated with siRNA directed against HIF-1alpha and HIF-2alpha displayed reduced proliferation, angiogenesis and apoptosis, cellular responses, which are known to be affected by HIF. In conclusion, intravenous jugular vein injection of siRNA strongly targets the lung tumor and is effective in gene inhibition as demonstrated for HIF-1alpha and HIF-2alpha.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Basic Helix-Loop-Helix Transcription Factors - antagonists and inhibitors Basic Helix-Loop-Helix Transcription Factors - biosynthesis Basic Helix-Loop-Helix Transcription Factors - genetics Basic Helix-Loop-Helix Transcription Factors - physiology
Carcinoma, Lewis Lung - genetics Carcinoma, Lewis Lung - pathology Carcinoma, Lewis Lung - therapy
Down-Regulation -
Gene Therapy - methods
Hypoxia-Inducible Factor 1, alpha Subunit - antagonists and inhibitors Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - physiology
Imines - administration and dosage
Injections, Intraperitoneal -
Injections, Intravenous -
Jugular Veins -
Lipids - administration and dosage
Lung Neoplasms - genetics Lung Neoplasms - pathology Lung Neoplasms - therapy
Mice -
Mice, Inbred C57BL -
Neoplasm Proteins - antagonists and inhibitors Neoplasm Proteins - biosynthesis Neoplasm Proteins - genetics Neoplasm Proteins - physiology
Neovascularization, Pathologic - therapy
Polyethylenes - administration and dosage
RNA Interference -
RNA, Small Interfering - administration and dosage RNA, Small Interfering - genetics RNA, Small Interfering - pharmacokinetics RNA, Small Interfering - therapeutic use
Specific Pathogen-Free Organisms -
Subcutaneous Tissue -
Trachea -

Find related publications in this database (Keywords)
RNA interference
polyethylenimine
orthotopic
lung cancer
mouse model
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