The effects of sirolimus on urothelial lesions chemically induced in ICR mice by BBN.
BACKGROUND
Sirolimus was originally used as an immunosuppressant drug but recent reports have indicated that it may have other potential biological effects as an anticancer drug. The chemopreventive efficacy of sirolimus was evaluated in an experimental model of invasive urinary bladder cancer.


METHODS
ICR mice received N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water for a period of twelve weeks. Sirolimus was administered 5 days a week. Animals were sacrificed either one or four weeks after their final treatment. Ki-67 was immunohistochemically analysed in paraffin-embedded tissue.


RESULTS
No evidence of host toxicity was found. The incidence of BBN-induced invasive urothelial carcinoma was significantly reduced in mice treated with sirolimus. Preneoplastic and neoplastic lesions exhibited a significant decrease in cellular proliferation.


CONCLUSIONS
Histopathological and immunohistochemical studies showed that sirolimus reduced tumour incidence and proliferation. Sirolimus should be considered for further in vitro and in vivo studies in order to provide evidence of effectiveness.
Oliveira
Paula A
PA
Department of Veterinary Sciences, CECAV, University of Trás-os-Montes and Alto Douro, 5001-801 Vila Real, Portugal. pamo@utad.pt
Arantes-Rodrigues
Regina
R
Sousa-Diniz
Clarisse
C
Colaço
Aura
A
Lourenço
Lígia
L
De La Cruz
Luis Felipe P
LF
Da Silva
Vítor Moreira
VM
Afonso
Julieta
J
Lopes
Carlos
C
Santos
Lúcio
L
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002085:Butylhydroxybutylnitrosamine / Q000633:toxicity*; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020123:Sirolimus / Q000494:pharmacology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000903:Antibiotics, Antineoplastic; D002085:Butylhydroxybutylnitrosamine; D020123:Sirolimus