Details

Autor(en) / Beteiligte

• Aleku, Manuela
• Schulz, Petra
• Keil, Oliver
• Santel, Ansgar
• Schaeper, Ute
• Dieckhoff, Britta
• Janke, Oliver
• Endruschat, Jens
• Durieux, Birgit
• Röder, Nadine
• Löffler, Kathrin
• Lange, Christian
• Fechtner, Melanie
• Möpert, Kristin
• Fisch, Gerald
• Dames, Sibylle
• Arnold, Wolfgang
• Jochims, Karin
• Giese, Klaus
• Wiedenmann, Bertram
• Scholz, Arne
• Kaufmann, Jörg

Titel

Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression

Ist Teil von

• Cancer research (Chicago, Ill.), 2008-12, Vol.68 (23), p.9788-9798

Ort / Verlag

United States

Erscheinungsjahr

2008

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• We have previously described a small interfering RNA (siRNA) delivery system (AtuPLEX) for RNA interference (RNAi) in the vasculature of mice. Here we report preclinical data for Atu027, a siRNA-lipoplex directed against protein kinase N3 (PKN3), currently under development for the treatment of advanced solid cancer. In vitro studies revealed that Atu027-mediated inhibition of PKN3 function in primary endothelial cells impaired tube formation on extracellular matrix and cell migration, but is not essential for proliferation. Systemic administration of Atu027 by repeated bolus injections or infusions in mice, rats, and nonhuman primates results in specific, RNAi-mediated silencing of PKN3 expression. We show the efficacy of Atu027 in orthotopic mouse models for prostate and pancreatic cancers with significant inhibition of tumor growth and lymph node metastasis formation. The tumor vasculature of Atu027-treated animals showed a specific reduction in lymph vessel density but no significant changes in microvascular density.