Anti-tumor effect of cimetidine via inhibiting angiogenesis factors in N-butyl-N-(4-hydroxybutyl) nitrosamine-induced mouse and rat bladder carcinogenesis
- Yoshitomo Chihara
- Kiyohide Fujimoto
- Makito Miyake
- Yoshio Hiasa
- Yoshihiko Hirao
Published online on: July 1, 2009
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.