Moser, Christian and Schachtschneider, Philipp and Lang, Sven A. and Gaumann, Andreas and Mori, Akira and Zimmermann, Johann and Schlitt, Hans J. and Geissler, Edward K. and Stoeltzing, Oliver (2008) Inhibition of insulin-like growth factor-I receptor (IGF-IR) using NVP-AEW541, a small molecule kinase inhibitor, reduces orthotopic pancreatic cancer growth and angiogenesis. EUROPEAN JOURNAL OF CANCER, 44 (11). pp. 1577-1586. ISSN 0959-8049,
Full text not available from this repository. (Request a copy)Abstract
The insulin-like growth factor-I receptor (IGF-IR) is frequently overexpressed and constitutively activated in pancreatic cancer, thus representing a promising target for therapy. We investigated the impact of a novel inhibitor of IGF-IR (NVP-AEW541) on signalling and growth of pancreatic cancer. Human pancreatic cancer cells and endothelial cells were employed, and effects of NVP-AEW541 on signalling pathways investigated by Western blotting. NVP-AEW541 diminished the activation of IGF-IR, IRS-1, Erk, Akt and STAT3. Furthermore, NVP-AEW541 reduced cancer cell proliferation and abrogated migratory effects of IGF-1. NVP-AEW541 elicited a direct effect on endothelial cells in terms of reducing endothelial cell migration. In vivo, treatment of mice with NVP-AEW541 significantly reduced orthotopic pancreatic tumour growth, vascularisation, and VEGF expression. Interestingly, NVP-AEW541 lowered serum levels of IGF-binding-protein-3 (IGFBP-3). In conclusion, the IGF-IR inhibitor NVP-AEW541 effectively disrupts IGF-I signalling and reduces pancreatic tumour growth. Hence, blocking IGF-IR could prove valuable for targeted therapy of pancreatic cancer. (c) 2008 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MYELOID-LEUKEMIA CELLS; TUMOR-GROWTH; MONOCLONAL-ANTIBODY; ANTITUMOR-ACTIVITY; AUTOCRINE LOOP; COLON-CANCER; VIVO; EXPRESSION; ACTIVATION; CARCINOMA; insulin-like growth factor-I receptor; IGF-binding-protein-3; VEGF; STAT3; angiogenesis; pancreatic cancer |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Oct 2020 09:43 |
| Last Modified: | 28 Oct 2020 09:43 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30653 |
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