The effect of H2 antagonists on proliferation and apoptosis in human colorectal cancer cell lines
The effect of H2 antagonists on proliferation and apoptosis in human colorectal cancer cell lines
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DOI：
10.1023/b:ddas.0000043377.30075.ac
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发表时间：
2004-10-01
影响因子：
3.1
通讯作者：
Kumar, P
中科院分区：
文献类型：
--
作者：
Rajendra, S;Mulcahy, H;Kumar, P
已知西咪替丁可提高胃肠道癌症患者的生存率，但其机制尚不完全清楚。假设的作用模式包括阻断肿瘤的增殖作用和抑制T抑制细胞活性，这两者都被认为是由组胺2型受体介导的。细胞凋亡可能为细胞生长减少提供了另一种解释。我们的目的是研究组胺、西咪替丁和雷尼替丁对两种人类结直肠癌细胞系Caco-2和LoVo体外增殖和凋亡的影响。细胞增殖试验作为细胞生长的指标。组胺受体状态通过定量环磷酸腺苷和DNA片段凋亡来确定。结果表明，组胺(10（-5)~ 10(-9)M）对两种细胞系的生长均无影响。雷尼替丁（10(-7)M）单独或联合组胺均能抑制Caco-2的增殖。西咪替丁（10(-5)M）仅在组胺存在时抑制Caco-2的生长。与组胺无关，H-2拮抗剂对LoVo无影响。在相同浓度的组胺作用下，Caco-2细胞中没有环磷酸腺苷的积累。两种抗分泌药物均可诱导Caco-2细胞凋亡，仅雷尼替丁引起LoVo细胞凋亡。我们得出结论，西咪替丁和雷尼替丁在体外抑制Caco-2癌细胞，独立于H2受体。此外，这两种药物在同一细胞系中诱导细胞凋亡。生长抑制和细胞凋亡可能是西咪替丁和雷尼替丁体内肿瘤消退的原因。
Cimetidine is known to enhance the survival of gastro-intestinal cancer patients, though the mechanisms involved are incompletely understood. Postulated modes of action include blocking the proliferative effect of tumors and inhibiting T suppressor cell activity, both of which are thought to be mediated by histamine type 2 receptors. Apoptotic cell death may offer an alternative explanation for reduced cell growth. We aimed to examine the effects of histamine, cimetidine, and ranitidine on in vitro proliferation and apoptosis in two human colorectal cancer cell lines, Caco-2 and LoVo. A cell proliferation assay was used as an index of cell growth. Histamine receptor status was determined by quantifying cyclic adenosine monophosphate and apoptosis via DNA fragmentation. Results show that histamine (10(-5) to 10(-9) M) had no effect on the growth of either cell line. The proliferation of Caco-2 was inhibited by ranitidine (10(-7) M) alone and in combination with histamine. Cimetidine (10(-5) M) only suppressed the growth of Caco-2 in the presence of histamine. The H-2 antagonists had no effect on LoVo irrespective of histamine. There was no accumulation of cyclic adenosine monophosphate in Caco-2 cells in response to histamine at a similar concentration. Apoptosis was induced in Caco-2 by both antisecretory drugs, and only ranitidine caused apoptotic cell death in LoVo cells. We conclude that cimetidine and ranitidine inhibit Caco-2 cancer cells in vitro, independently of the H2 receptor. In addition, both drugs induce apoptosis in the same cell line. Growth inhibition and apoptosis are likely to contribute to the tumor regressive properties of cimetidine and ranitidine in vivo.