FTY720 and lung tumor development.
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 urethane intraperitoneally in two doses of 1.5 g/kg 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 the number of leukocyte in blood, lymphocytes in spleen, and lungs were evaluated for changes in histology, PCNA and VEGF 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. G1 and G4 groups presented the lower number of splenocytes and neutrophils. In early time FTY720 treated mice (G2) we observed a slight decrease in PCNA staining and also the lower percentage of VEGF intense staining. Therefore, our data suggest that the benefits of FTY720 treatment are time-dependent and when administered in early periods after lung tumor induction this drug could impair cancer development.
Salinas
Natália Regina Antunes
NR
Division of Immunology, UNIFESP-Federal University of São Paulo, R. Botucatu 862, São Paulo, Brazil.
Oshima
Celina Tizuko Fujiyama
CT
Cury
Patrícia Maluf
PM
Cordeiro
José Antonio
JA
Bueno
Valquiria
V
D000236:Adenoma / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology / Q000378:metabolism; D011409:Propylene Glycols / Q000008:administration & dosage*; D013110:Sphingosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014520:Urethane / Q000633:toxicity; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology / Q000378:metabolism
D007166:Immunosuppressive Agents; D018809:Proliferating Cell Nuclear Antigen; D011409:Propylene Glycols; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D014520:Urethane; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine