Van der Ven L T, Prinsen I M, Jansen G H, Roholl P J, Defferrari R, Slater R, Den Otter W
Department of Pathology, Academisch Ziekenhuis Utrecht, The Netherlands.
Br J Cancer. 1993 Sep;68(3):475-83. doi: 10.1038/bjc.1993.373.
The 50% survival time for low grade astrocytomas is 50 months and for high grade astrocytomas it is 13 months, underlining the need for new therapies. Several reports show that in vivo histamine antagonists cause retardation of tumour growth in some animal models and prolonged survival in cancer patients. Therefore we have tested the growth modulating effects of histamine and histamine antagonists on human glioma cultures. Twelve freshly excised human gliomas were cultured and tested for their in vitro sensitivity to histamine and histamine antagonists. Four continuous glioma cell lines were used to confirm the glioma-specificity of the effects observed in the primary cell lines. In low serum concentration (0 or 1%) the growth of 5/9 primary glioma-derived cultures could be stimulated with 0.2 mM histamine, and in 4/5 cases with 0.2 microM histamine. One mM of the histamine H2-receptor antagonist cimetidine could inhibit the growth of 4/5 primary glioma cultures when tested in 1% human AB serum, and of 6/13 cases when tested in 1% FCS. Lower concentrations (down to 1 microM) were less effective. The histamine H1-receptor antagonist pyrilamine gave variable results. The specificity of the effects is indicated by the absence of a generalised toxic effect, by the observation that the antagonist-induced inhibition could be reversed with histamine, and by the correlation of the obtained cimetidine-induced growth inhibition with the maximal growth rate of the primary cell lines in 10% FCS. The observed cimetidine-induced inhibition of the in vitro proliferation of gliomas suggests that cimetidine is a relevant candidate for the in vivo growth inhibition of these tumours.
低级别星形细胞瘤的50%生存时间为50个月，高级别星形细胞瘤则为13个月，这凸显了对新疗法的需求。多项报告显示，在一些动物模型中，体内组胺拮抗剂可使肿瘤生长延缓，并使癌症患者生存期延长。因此，我们测试了组胺和组胺拮抗剂对人胶质瘤培养物的生长调节作用。对12例新鲜切除的人胶质瘤进行培养，并测试其对组胺和组胺拮抗剂的体外敏感性。使用4种连续胶质瘤细胞系来确认在原代细胞系中观察到的效应的胶质瘤特异性。在低血清浓度（0%或1%）下，0.2 mM组胺可刺激5/9原代胶质瘤衍生培养物的生长，0.2 μM组胺可刺激4/5的培养物生长。在1%人AB血清中测试时，1 mM组胺H2受体拮抗剂西咪替丁可抑制4/5原代胶质瘤培养物的生长，在1%胎牛血清中测试时，可抑制6/13的培养物生长。较低浓度（低至1 μM）效果较差。组胺H1受体拮抗剂吡苄明的结果不一。这些效应的特异性体现在无普遍毒性作用、拮抗剂诱导的抑制作用可被组胺逆转，以及西咪替丁诱导的生长抑制与原代细胞系在10%胎牛血清中的最大生长速率之间的相关性。观察到西咪替丁对胶质瘤体外增殖的抑制作用表明，西咪替丁是体内抑制这些肿瘤生长的一个相关候选药物。
