Journal article

Publication year: 2009

Pages: 195-205

Journal: Cancer Gene Therapy

Volume number: 16

Issue number: 3

ISSN: 0929-1903

eISSN: 1476-5500

DOI Link: https://doi.org/10.1038/cgt.2008.71

Publisher: Springer Nature [academic journals on nature.com]

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-1 alpha and HIF-2 alpha). 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-1 alpha and HIF-2 alpha 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-1 alpha and HIF-2 alpha, compared with mice treated with control siRNA. Interestingly, injection of siRNA directed against HIF-1 alpha and HIF-2 alpha into LLC1 lung tumor-bearing mice resulted in prolonged survival. Immunohistological analysis of the lung tumors from mice treated with siRNA directed against HIF-1 alpha and HIF-2 alpha 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-1 alpha and HIF-2 alpha.

Harvard Citation style: Kamlah, F., Eul, B., Li, S., Lang, N., Marsh, L., Seeger, W., et al. (2009) Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model, Cancer Gene Therapy, 16(3), pp. 195-205. https://doi.org/10.1038/cgt.2008.71

APA Citation style: Kamlah, F., Eul, B., Li, S., Lang, N., Marsh, L., Seeger, W., Grimminger, F., Rose, F., & Haenze, J. (2009). Intravenous injection of siRNA directed against hypoxia-inducible factors prolongs survival in a Lewis lung carcinoma cancer model. Cancer Gene Therapy. 16(3), 195-205. https://doi.org/10.1038/cgt.2008.71