Cimetidine inhibits angiogenesis and suppresses tumor growth.
Cimetidine, a histamine type-2 receptor antagonist, has been reported to improve survival of patients with cancers. However, the exact mechanisms by which cimetidine suppresses development of cancers remain to be elucidated. Solid tumors require neovascularization for their growth. Here, we investigated the effects of cimetidine on tumor growth and angiogenesis. Syngeneic colon cancer cells, CMT93 cells, were inoculated into the subcutaneous space of C57BL/6 mice. Mice were treated with either saline or cimetidine. Tumor size was measured everyday and angiogenesis was evaluated histologically. Cimetidine markedly suppressed tumor growth with reduced neovascularization in the tumor. Cimetidine had no effect on proliferation of CMT93 cells in vitro. Vascular endothelial growth factor production by cancer cells was not affected by cimetidine, while vascular-like tube formation by endothelial cells in vitro was significantly impaired in the presence of cimetidine. Our findings suggest that cimetidine suppresses tumor growth, at least in part, by inhibiting tumor-associated angiogenesis.
Natori
Takeshi
T
Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo 113-8655, Japan.
Sata
Masataka
M
Nagai
Ryozo
R
Makuuchi
Masatoshi
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002927:Cimetidine / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006131:Growth Inhibitors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000517:prevention & control*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D002927:Cimetidine