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


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.


CONCLUSIONS
These findings suggest that BGP-15 suppresses hepatoma development by affecting angiogenesis.
Kardon
Tamás
T
Department of Medical Chemistry, Semmelweis University, 1444 Budapest P.O.B. 260, Hungary.
Nagy
Gábor
G
Csala
Miklós
M
Kiss
András
A
Schaff
Zsuzsa
Z
Nagy
Péter Literáti
PL
Wunderlich
Livius
L
Bánhegyi
Gábor
G
Mandl
József
J
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D005260:Female; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008938:Mitosis / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010091:Oximes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D051272:Glucose Transporter Type 1; D010091:Oximes; D010880:Piperidines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C405586:BGP 15