Halofuginone inhibits angiogenesis and growth in implanted metastatic rat brain tumor model--an MRI study.
Tumor growth and metastasis depend on angiogenesis; therefore, efforts are made to develop specific angiogenic inhibitors. Halofuginone (HF) is a potent inhibitor of collagen type alpha1(I). In solid tumor models, HF has a potent antitumor and antiangiogenic effect in vivo, but its effect on brain tumors has not yet been evaluated. By employing magnetic resonance imaging (MRI), we monitored the effect of HF on tumor progression and vascularization by utilizing an implanted malignant fibrous histiocytoma metastatic rat brain tumor model. Here we demonstrate that treatment with HF effectively and dose-dependently reduced tumor growth and angiogenesis. On day 13, HF-treated tumors were fivefold smaller than control (P < .001). Treatment with HF significantly prolonged survival of treated animals (142%; P = .001). In HF-treated rats, tumor vascularization was inhibited by 30% on day 13 and by 37% on day 19 (P < .05). Additionally, HF treatment inhibited vessel maturation (P = .03). Finally, in HF-treated rats, we noticed the appearance of a few clusters of satellite tumors, which were distinct from the primary tumor and usually contained vessel cores. This phenomenon was relatively moderate when compared to previous reports of other antiangiogenic agents used to treat brain tumors. We therefore conclude that HF is effective for treatment of metastatic brain tumors.
Abramovitch
Rinat
R
The Goldyne Savad Institute of Gene Therapy, MRI/MRS Laboratory, HBRC, Hadassah Hebrew University Medical Center, Jerusalem, Israel. rinat@hadassah.org.il
Itzik
Anna
A
Harel
Hila
H
Nagler
Arnon
A
Vlodavsky
Israel
I
Siegal
Tali
T
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018219:Histiocytoma, Benign Fibrous / Q000473:pathology; D008279:Magnetic Resonance Imaging; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D010880:Piperidines; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones; D051381:Rats
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010880:Piperidines; D011799:Quinazolines; D052999:Quinazolinones; C010176:halofuginone