Effect of glibenclamide on N-nitroso-N-methylurea-induced mammary tumors in diabetic and nondiabetic rats.
The objective of this study was to evaluate the antitumor effect of glibenclamide (Gli) alone or in combination with tamoxifen (Tam) on experimental mammary tumors induced by N-nitroso-N-methylurea (NMU) in nondiabetic and diabetic rats. For experimental diabetes induction, Sprague-Dawley rats were injected with streptozotocin (STZ) on the second day of life. For experimental mammary tumor induction, nondiabetic and diabetic rats were injected IP with NMU at 50, 80, and 110 days of life. Nondiabetic and diabetic rats bearing mammary tumors were treated with 0.06 mg/day of Gli orally, Tam 1 mg/kg/day SC, or with the combined treatment (Gli + Tam). After 20 days of treatment, different responses were observed. In nondiabetic rats, 64% of tumors were responsive to Gli treatment (they regressed or remained stable), whereas 57% of tumors under treatment with Tam exhibited a response. Results of the combined Gli + Tam treatment indicated that all tumors were responsive: 58% regressed and 42% remained stable. Diabetic rats receiving Gli treatment did not show response to this treatment, while 65% of the tumors of Tam-treated diabetic rats showed regression. Histopathologic observation indicated an important intratumor secretion in all tumors of Gli-, Tam-, or Gli + Tam-treated rats. No secondary toxic effect was observed after treatment at any assayed doses. In conclusion, the present data demonstrate the in vivo antitumor action of Gli treatment on the experimental mammary tumors employed, indicating that Gli exerted a direct effect on tumor cells in nondiabetic rats. The combined Gli + Tam treatment potentiated the antitumor effect of each drug alone. Future research will examine the molecular aspects of these findings.
Cocca
Claudia
C
Radioisotopes Laboratory, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina.
Martín
Gabriela
G
Núñez
Mariel
M
Gutiérrez
Alicia
A
Cricco
Graciela
G
Mohamad
Nora
N
Medina
Vanina
V
Croci
Máximo
M
Crescenti
Ernesto
E
Rivera
Elena
E
Bergoc
Rosa
R
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D004347:Drug Interactions; D005260:Female; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008770:Methylnitrosourea; D051381:Rats; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000008:administration & dosage
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D013629:Tamoxifen; D008770:Methylnitrosourea; D005905:Glyburide