Watson S A, Wilkinson L J, Robertson J F, Hardcastle J D
Cancer Research Campaign Laboratories, University of Nottingham.
Gut. 1993 Aug;34(8):1091-6. doi: 10.1136/gut.34.8.1091.
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.
研究了组胺对人胃肿瘤细胞系（产胃泌素亚系MKN45、MKN45G）以及结肠癌细胞系（LoVo和C170）的增殖作用。通过75[Se]硒代蛋氨酸摄取和细胞计数评估，10(-7) M和10(-9) M的组胺浓度可增加MKN45的增殖。10(-6) M至10(-7) M之间的组胺浓度可最大程度刺激MKN45G的增殖，而在较低组胺浓度下这种刺激作用逐渐减弱。在这两种胃细胞系中，相同组胺浓度下的环磷酸腺苷（cAMP）积累也有所增加。组胺受体拮抗剂西咪替丁（10(-5) M）可逆转组胺对两种胃细胞系增殖的刺激作用，尽管它对基础生长没有影响。结肠癌细胞系的增殖不受组胺影响。在肿瘤皮下植入部位局部给予组胺（1 mg/kg/天）可增加裸鼠体内MKN45G异种移植物的生长。同时给予西咪替丁（100 mg/kg/天，通过饮用水给予）可逆转这种作用。西咪替丁还可抑制MKN45异种移植物的基础增殖。局部作用的组胺可能会增强胃内肿瘤的增殖。给予组胺受体拮抗剂（如西咪替丁）可能会阻断这种作用。
