Influence of BGP-15, a nicotinic amidoxime derivative, on the vascularization and growth of murine hepatoma xenografts.

Abstract

BACKGROUND:

The expression of vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is controlled by the oxygen supply. Previous observations suggested that nicotinic amidoxime derivatives (i.e. BGP-15) might interfere with the induction of hypoxia-sensitive genes. Hence, the effect of BGP-15 on angiogenesis was studied in Hepa 1c1c7 tumor xenografts.

MATERIALS AND METHODS:

Hepa 1c1c7 hepatoma cells were implanted under the dorsal skin of female CD-1-nu/nu immunodeficient mice. One group of animals was given 100 mg/kg body weight/day BGP-15 intraperitoneally during tumor development. Vascularization, apoptotic and mitotic indices were determined by the histological and immunohistochemical analysis of the tumors. VEGF and GLUT-1 expressions were measured by Northern blot.

RESULTS:

The in vivo administration of BGP-15 resulted in a decrease in tumor weight and mitotic index, while it did not affect the apoptotic rate in the xenograft. Furthermore, BGP-15 treatment depressed microvascular density and the level of VEGF mRNA by 50%, and similarly decreased GLUT-1 mRNA levels.

CONCLUSION:

These findings suggest that BGP-15 suppresses hepatoma development by affecting angiogenesis.

• Authors: Tamás Kardon, Gábor Nagy, Miklós Csala, András Kiss, Zsuzsa Schaff, Péter Literáti Nagy, Livius Wunderlich, Gábor Bánhegyi, József Mandl
• Journal: Anticancer research (Anticancer Res) 2006 Mar-Apr Vol. 26 Issue 2A Pg. 1023-8 ISSN: 0250-7005 [Print] Greece
• PMID: 16619502 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 1
• Oximes
• Piperidines
• RNA, Messenger
• Vascular Endothelial Growth Factor A
• BGP 15

Topics

• Animals
• Apoptosis (drug effects)
• Cell Growth Processes (drug effects)
• Female
• Glucose Transporter Type 1 (biosynthesis, genetics)
• Liver Neoplasms, Experimental (blood supply, drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Mitosis (drug effects)
• Neovascularization, Pathologic (drug therapy, metabolism, pathology)
• Oximes (pharmacology)
• Piperidines (pharmacology)
• RNA, Messenger (biosynthesis, genetics)
• Vascular Endothelial Growth Factor A (biosynthesis, genetics)
• Xenograft Model Antitumor Assays