Targeting the insulin-like growth factor-1 receptor by picropodophyllin as a treatment option for glioblastoma.
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.
Yin
Shucheng
S
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, 17176 Stockholm, Sweden.
Girnita
Ada
A
Strömberg
Thomas
T
Khan
Zahidul
Z
Andersson
Sandra
S
Zheng
Huiyuan
H
Ericsson
Christer
C
Axelson
Magnus
M
Nistér
Monica
M
Larsson
Olle
O
Ekström
Tomas J
TJ
Girnita
Leonard
L
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D016513:Mice, SCID; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C415032:picropodophyllin; D017526:Receptor, IGF Type 1; D011034:Podophyllotoxin