[组胺H2受体激动剂、拮抗剂及抗肿瘤药物对正常个体外周血CFU-GM及HL-60白血病细胞体外生长的影响]
[The effects of histamine H2 receptor agonist, antagonist and antineoplastic agent on the in vitro growth of PB CFU-GM from normal individuals and HL-60 leukemia cells].
作者信息
He Q, Xu Y H
机构信息
Research Laboratory of Blood Physiology, Human Medical University, Changsha.
出版信息
Yao Xue Xue Bao. 1996;31(5):340-5.
Colony forming unit of granulocytes and macrophages from peripheral blood (PB CFU-GM) represents stem and/or progenitor cells from human blood. In this paper, the effects of histamine H2 receptor agonist 4-methylhistamine (4-MH) and its antagonist ranitidine (Ranit) on the growth of PB CFU-GM cultured in methylcellulose system were studied and their differential effects on normal PB CFU-GM and leukemic HL-60 cells were compared with the effect of the antineoplastic agent cytosine arabinoside (Ara-C). It was found that the histamine H2 receptor agonist 4-MH stimulated the growth of PB CFU-GM when 4-MH was added at the concentrations from 10(-9) mol.L-1 to 10(-6) mol.L-1 among which the dose 10(-8) mol.L-1 exerted most potent stimulating effect (the PB CFU-GM colony numbers was 137.68% +/- 8.20% vs the control, P < 0.01). In contrast, the antagonist Ranit showed inhibitory effect on the growth of PB CFU-GM when at the concentrations 10(-9)-10(-5) mol.L-1 cultured for 14 d in the same methylcellulose system. The inhibition rate was 23.73% +/- 1.16% (10(-9) mol.L-1) and 41.42% +/- 6.75% (10(-6) mol.L-1), respectively. Although both Ranit and Ara-C could inhibit the growth of PB CFU-GM in vitro, Ranit exerted much greater inhibition on HL-60 leukemic cells than on normal PB CFU-GM at the dose of 10(-6) mol.L-1 (100% inhibition for HL-60 and < 50% inhibition for PB CFU-GM). However, the inhibition rate of Ara-C for both HL-60 and PB CFU-GM was 100% at the intensive chemotherapeutic dose of 10(-5) mol.L-1. It would appear that the histamine H2 receptor agonist 4-MH possesses stimulating effect on the growth of PB CFU-GM similar to its effect on CFU-GM from bone marrow as documented before. It is suggested that the histamine H2 receptor antagonist Ranit has, to some extent, potential in the treatment of myeloid leukemia, especially when combined with antineoplastic agent Ara-C at suboptimal doses.
外周血粒细胞和巨噬细胞集落形成单位（PB CFU - GM）代表人类血液中的干细胞和/或祖细胞。本文研究了组胺H2受体激动剂4 - 甲基组胺（4 - MH）及其拮抗剂雷尼替丁（Ranit）对甲基纤维素体系中培养的PB CFU - GM生长的影响，并将它们对正常PB CFU - GM和白血病HL - 60细胞的差异作用与抗肿瘤药物阿糖胞苷（Ara - C）的作用进行了比较。结果发现，当4 - MH以10^(-9) mol·L^(-1)至10^(-6) mol·L^(-1)的浓度添加时，组胺H2受体激动剂4 - MH刺激了PB CFU - GM的生长，其中10^(-8) mol·L^(-1)的剂量产生了最显著的刺激作用（PB CFU - GM集落数为137.68%±8.20%，与对照组相比，P < 0.01）。相反，在相同的甲基纤维素体系中培养14 d时，拮抗剂Ranit在10^(-9) - 10^(-5) mol·L^(-1)的浓度下对PB CFU - GM的生长显示出抑制作用。抑制率分别为23.73%±1.16%（10^(-9) mol·L^(-1)）和41.42%±6.75%（10^(-6) mol·L^(-1)）。尽管Ranit和Ara - C在体外都能抑制PB CFU - GM的生长，但在10^(-6) mol·L^(-1)的剂量下，Ranit对HL - 60白血病细胞的抑制作用比对正常PB CFU - GM的抑制作用大得多（对HL - 60的抑制率为100%，对PB CFU - GM的抑制率<50%）。然而，在10^(-5) mol·L^(-1)的强化化疗剂量下，Ara - C对HL - 60和PB CFU - GM的抑制率均为100%。似乎组胺H2受体激动剂4 - MH对PB CFU - GM的生长具有刺激作用，类似于其对骨髓CFU - GM的作用，如之前所报道的。提示组胺H2受体拮抗剂Ranit在一定程度上具有治疗髓系白血病的潜力，特别是与次优剂量的抗肿瘤药物Ara - C联合使用时。
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