Inhibition of experimental U-118MG glioblastoma by targeted cytotoxic analogs of bombesin and somatostatin is associated with a suppression of angiogenic and antiapoptotic mechanisms.

Abstract	Human gliomas express receptors for bombesin and somatostatin that can be used for targeted chemotherapy. In the present study, the efficacy and the mechanism of action of cytotoxic bombesin analog AN-215, and cytotoxic somatostatin analog AN-238 were investigated in U-118MG human glioblastomas xenografted into nude mice. The expression of vascular endothelial growth factor (VEGF) and the apoptotic markers Bcl-2 and Bax was analyzed by Western blotting. The toxicity was evaluated by measuring leukocyte levels and body weights. Treatment with AN-215 or AN-238 reduced tumor growth by approximately 50%, and diminished the levels of VEGF by 45 and 75%, respectively. The relative ratio of Bcl-2 to Bax proteins was decreased by approximately 90%, indicating a net apoptotic gain and efficacy of treatment. Specific receptors for bombesin and somatostatin were found in U-118MG tumors. Our results suggest that targeted cytotoxic analogs, AN-215 and AN-238, could be useful for the treatment of human glioblastomas.
Authors	Celia A Kanashiro, Andrew V Schally, Attila Nagy, Gabor Halmos
Journal	International journal of oncology (Int J Oncol) Vol. 27 Issue 1 Pg. 169-74 (Jul 2005) ISSN: 1019-6439 [Print] Greece
PMID	15942657 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References	BAX protein, human Bax protein, mouse Hormones Peptides Proto-Oncogene Proteins c-bcl-2 Receptors, Bombesin Receptors, Somatostatin Vascular Endothelial Growth Factor A bcl-2-Associated X Protein Somatostatin Bombesin
Topics	Animals Apoptosis Blotting, Western Body Weight Bombesin (pharmacology) Cell Line, Tumor Cell Proliferation Glioblastoma (drug therapy, pathology) Hormones (metabolism) Humans Kinetics Male Mice Mice, Nude Neoplasm Transplantation Neovascularization, Pathologic Peptides (chemistry) Protein Binding Proto-Oncogene Proteins c-bcl-2 (metabolism) Receptors, Bombesin (metabolism) Receptors, Somatostatin (metabolism) Somatostatin (pharmacology) Time Factors Vascular Endothelial Growth Factor A (metabolism) bcl-2-Associated X Protein

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!