FTY720 treatment in experimentally urethane-induced lung tumors.
FTY720 has been shown to prevent cancer development in experimental models but there is no report whether this beneficial effect is associated with the time point of the drug administration. Lung adenoma was induced in mice by urethane injection followed by different periods of FTY720 administration in order to evaluate lung tumor development. BALB/c mice received two doses (1, 5 g/kg) of urethane intraperitoneally and were submitted to five daily doses of FTY720 (1 mg/kg/day) starting just after urethane injection (G2 n=5), 4 weeks after urethane injection (G3 n=10), 8 weeks after urethane injection (G4 n=10) and no FTY720 administration (G1 n=5). Twenty-four weeks after urethane administration mice were evaluated for leukocyte numbers in blood, lymphocytes in spleen, and lungs were evaluated for changes in histology and PCNA expression. Lung nodules were present in higher numbers both in non treated (G1; 0.0-7.0) and FTY720 treated 8 weeks after urethane injection (G4; 0.0-6.0). G4 Group also presented the highest number of papillary nodules. There was a decrease in PCNA staining in early time FTY720 treated mice. Therefore, our data suggest that FTY720 treatment in early periods after lung tumor induction is beneficial and impairs adenoma development.
Lucas da Silva
Léa Bueno
LB
Division of Immunology, FAMERP Sao Jose do Rio Preto Medical School, Brazil.
Ribeiro
Daniel Araki
DA
Cury
Patrícia Maluf
PM
Cordeiro
José Antonio
JA
Bueno
Valquiria
V
D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002273:Carcinogens; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008175:Lung Neoplasms / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011409:Propylene Glycols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000166:cytology; D014520:Urethane
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D011409:Propylene Glycols; D014520:Urethane; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine