The proliferative effects of histamine were examined on the human gastric tumour cell lines; MKN45, the gastrin producing subline, MKN45G, and the colorectal lines; LoVo and C170. The proliferation of MKN45 as assessed by 75[Se] selenomethionine uptake and cell counts was increased by histamine concentrations of 10(-7) and 10(-9) M. Histamine concentrations between 10(-6) and 10(-7) M maximally stimulated MKN45G proliferation which titrated out at lower histamine concentrations. The accumulation of cyclic adenosine 3',5' monophosphate (cAMP) in response to the same histamine concentrations was also increased in the two gastric cell lines. The histamine receptor antagonist, cimetidine (10(-5) M) reversed the histamine stimulated proliferation of both gastric cell lines despite having no effect on basal growth. The proliferation of the colorectal lines was unaffected by histamine. Histamine given locally at the subcutaneous implantation site of the tumour (1 mg/kg/day) increased the growth of MKN45G xenografts in nude mice. This was reversed by coadministration of cimetidine (100 mg/kg/day, given in the drinking water). Cimetidine also inhibited the basal proliferation of MKN45 xenografts. Histamine acting locally may enhance the proliferation of tumours arising within the stomach. Such effects may be blocked by administration of histamine receptor antagonists, such as cimetidine.
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