Effect of rosiglitazone on N-nitroso-N-methylurea-induced mammary tumors in rat.
The objective of this study was to evaluate the in vivo antitumor action of rosiglitazone (Rosi) alone or in combination with tamoxifen (Tam) on experimental mammary tumors induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Animals bearing mammary tumors were treated with 0.06 mg/kg/day or 0.12 mg/kg/day of Rosi orally, 1 mg/kg/day of Tam s.c., or with the combined treatment (Rosi+Tam). After 25 days of treatment, the following responses were observed: 45% of tumors were responsive to 0.06 mg/kg/day of Rosi treatment, while 55% of tumors under Tam treatment responded. The results of the combined Rosi+Tam treatment indicated that 75% of tumors were responsive. Similar results were obtained with 0.12 mg/kg/day of Rosi. Apoptosis, necrosis and glandular hypersecretion were observed in Rosi-treated tumors. In all cases, the combined Rosi+Tam treatment potentiated the antitumor effect of Tam alone. No side-effects were observed after treatment at any assayed dose.
Núñez
Mariel
M
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Martín
Gabriela
G
Cocca
Claudia
C
Mohamad
Nora
N
Gutiérrez
Alicia
A
Cricco
Graciela
G
Medina
Vanina
V
Rivera
Elena
E
Croci
Máximo
M
Crescenti
Ernesto
E
Bergoc
Rosa
R
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005260:Female; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008770:Methylnitrosourea; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D013629:Tamoxifen / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*
D007328:Insulin; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013629:Tamoxifen; D007334:Insulin-Like Growth Factor I; D008770:Methylnitrosourea