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Neuro-Oncology Advance Access published online on October 20, 2009
Neuro-Oncology, doi:10.1093/neuonc/nop008
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© The Author(s) 2009. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma

Shucheng Yin*, Ada Girnita*, Thomas Strömberg*, Zahidul Khan, Sandra Andersson, Huiyuan Zheng, Christer Ericsson, Magnus Axelson, Monica Nistér, Olle Larsson, Tomas J. Ekström and Leonard Girnita

Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden (S.Y., A.G., T.S., S.A., H.Z., C.E., M.N., O.L., L.G.); Department of Otolaryngology and Head and Neck Surgery, Zhongnan Hospital, Wuhan University, 430071 Wuhan, People's Republic of China (S.Y.); Department of Clinical Neuroscience, Karolinska Institutet (Z.K., T.J.E.); Department of Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital (M.A.), Stockholm, Sweden

Corresponding Author: Thomas Strömberg, MD, PhD, Department of Oncology-Pathology, Karolinska Institutet, CCK R8:04, 17176 Stockholm, Sweden (thomas.stromberg{at}ki.se).


  Abstract

Glioblastoma (GB) is the most common malignant brain tumor in adults. It has limited treatment opportunities and is almost exclusively fatal. Owing to the central role the insulin-like growth factor-1 receptor (IGF-1R) plays in malignant cells, it has been suggested as a target for anticancer therapy including GB. The cyclolignan picropodophyllin (PPP) inhibits IGF-1R without affecting the highly homologous insulin receptor. Here, we show that PPP inhibits growth of human GB cell lines along with reduced phosphorylation of IGF-1R and AKT. In vivo, PPP-treatment causes dramatic tumor regression not only in subcutaneous xenografts but also in intracerebral xenografts, indicating passage of PPP across the blood-brain barrier.

Keywords: glioblastoma, glioma, IGF-1 receptor, picropodophyllin

Received January 23, 2009; Accepted April 23, 2009

* These authors have contributed equally.


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