Investigation of an inhibitor of lipid peroxidation U74006F on tumor growth and protein extravasation in the C6 astrocytoma spheroid implantation glioma model.
The role played by lipid peroxidation in cerebral tumor growth and protein extravasation has not been defined. A potent in vitro inhibitor of lipid peroxidation (21-[4-(2,6-di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16a- methylpregna-1,4,9(11)-triene-3,20-dione monomethane sulfonate (U74006F), has been used to assess its influence on both tumor growth and protein extravasation in a rat C6 astrocytoma implantation model. Following spheroid implantation, rats were treated with one of these U74006F regimens: 12 mg/kg/day for 13 days post-implantation, 3.6 mg/kg/day for 13 days post-implantation or 12 mg/kg/day commencing seven days post-implantation until 13 days post-implantation. Tumor wet weights, dry weight and protein flux as measured by Evans blue dye extravasation were assessed. Neither wet weights nor dry weights of any of the three treatment groups was significantly lower when compared to control tumor wet weights and dry weights. Protein extravasation was not significantly reduced by any of the treatments. It is concluded that U74006F did not significantly decrease tumor growth or permeability in the C6 astrocytoma spheroid implantation model.
Megyesi
J F
JF
Department of Clinical Neurological Sciences, University of Western Ontario, Victoria Hospital, London, Canada.
Farrell
C L
CL
Del Maestro
R F
RF
D000818:Animals; D001254:Astrocytoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011281:Pregnatrienes / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D009363:Neoplasm Proteins; D011281:Pregnatrienes; C053355:tirilazad