Anti-tumor effect of cimetidine via inhibiting angiogenesis factors in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced mouse and rat bladder carcinogenesis.
The aim of this study was to assess the anti-tumor effect and mechanisms of cimetidine in N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis model. Sixty-three male BALB/c mice and 67 male Wister rats were treated with BBN and cimetidine to examine the anti-tumor effect of cimetidine. Immunohistochemistry (IHC) of vascular endothelial growth factor (VEGF), platelet-derived endothelial growth factor (PDECGF), and E-selectin were examined to compare their expression in the tumor tissues. In mice, the tumor growth was reduced by cimetidine (p=0.011). The expression of PDECGF was reduced in the cimetidine-treated group (p=0.016). In rats, treatment of cimetidine reduced tumor growth (p=0.0001). Moreover, the expression of VEGF and PDECGF was reduced (p=0.02 and <0.001, respectively). The expression of E-selectin did not correlate with the tumor growth in either mice or rats. In mice, long-term cimetidine treatment proved very effective for inhibiting the tumor growth, but in rats, BBN after treatment with cimetidine showed the least tumor growth-inhibitory effect. In conclusion, cimetidine may have an inhibitory effect on tumor growth in bladder carcinogenesis via reducing the expression of angiogenesis factors including VEGF and PDECGF.
Chihara
Yoshitomo
Y
Department of Urology, Nara Medical University, Kashihara, Nara, Japan. yychihara@gmail.com
Fujimoto
Kiyohide
K
Miyake
Makito
M
Hiasa
Yoshio
Y
Hirao
Yoshihiko
Y
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002927:Cimetidine / Q000494:pharmacology*; D015536:Down-Regulation; D019040:E-Selectin / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009367:Neoplasm Staging; D051381:Rats; D017208:Rats, Wistar; D013939:Thymidine Phosphorylase / Q000378:metabolism; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D042501:Angiogenic Proteins; D019040:E-Selectin; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C467498:vascular endothelial growth factor A, rat; D002085:Butylhydroxybutylnitrosamine; D002927:Cimetidine; D013939:Thymidine Phosphorylase