[Impact of cimetidine on growth and metastasis of surgically transplanted Lewis lung cancer].
OBJECTIVE
Histamine has multiple biological functions and its immunomodulatory actions are not fully understood. In the current study, we investigated the effect of cimetidine, which is a histamine-2 receptor antagonist, on the progress of transplanted Lewis lung cancers using a mouse model.


METHODS
A piece of Lewis lung cancer weighing 15 mg was transplanted into the subcutaneous space on the back of each C 57 BL/6 mouse. Mice were randomized into a no-treatment control group (CO) or one of two treatment groups. In the treatment groups, 16 mg/kg/day (LD) or 160 mg/kg/day (HD) of cimetidine was orally administered from one week before the day of transplantation to the time of sacrifice. Subcutaneous tumors and lungs were excised on the 28th or 42nd postoperative day.


RESULTS
The mean vascular densities of the subcutaneous tumors on day 28 were 55.7 +/- 23.9/mm2 in CO, 88.0 +/- 16.3/mm2 in LD and 122.6 +/- 16.9/mm2 in HD (p < 0.05; CO vs. LD or HD, LD vs. HD). On day 42, mean weights of the subcutaneous tumors and the numbers of metastatic lung tumors were 6.0 +/- 2.1 g in CO, 7.9 +/- 1.2 g in LD and 10.0 +/- 1.9 g in HD (p < 0.05; CO vs. HD), and 7.5 +/- 6.0 in CO, 17.0 +/- 3.0 in LD and 19.8 +/- 7.4 in HD (p < 0.05; CO vs. HD), respectively.


CONCLUSIONS
These results suggest that cimetidine dose-dependently enhances the angiogenesis, growth and metastasis of surgically transplanted Lewis lung cancer in a mouse model of this type.
Suga
Michiharu
M
Department of Cardiovascular and Respiratory Surgery, Saitama Medical School.
Morita
Riichiro
R
Kaneko
Koichi
K
Kyo
Shunei
S
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D002927:Cimetidine / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000556:secondary*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology*
D002927:Cimetidine