何群, 徐有恒. 组胺H2受体激动剂和拮抗剂及抗癌药对正常人造血祖细胞和HL-60白血病细胞生长的作用J. 药学学报, 1996, 31(5): 340-345.
引用本文: 何群, 徐有恒. 组胺H2受体激动剂和拮抗剂及抗癌药对正常人造血祖细胞和HL-60白血病细胞生长的作用J. 药学学报, 1996, 31(5): 340-345.
Q He, YH Xu. THE EFFECTS OF HISTAMINE H2 RECEPTOR AGONIST,ANTAAGONIST AND ANTINEOPLASTIC AGENT ON THE IN VITRO GROWTH OF PB CFU-GM FROM NORMAL INDIVIDUALS AND HL-60 LEUKEMIA CELLSJ. Acta Pharmaceutica Sinica, 1996, 31(5): 340-345.
Citation: Q He, YH Xu. THE EFFECTS OF HISTAMINE H2 RECEPTOR AGONIST,ANTAAGONIST AND ANTINEOPLASTIC AGENT ON THE IN VITRO GROWTH OF PB CFU-GM FROM NORMAL INDIVIDUALS AND HL-60 LEUKEMIA CELLSJ. Acta Pharmaceutica Sinica, 1996, 31(5): 340-345.

组胺H2受体激动剂和拮抗剂及抗癌药对正常人造血祖细胞和HL-60白血病细胞生长的作用

THE EFFECTS OF HISTAMINE H2 RECEPTOR AGONIST,ANTAAGONIST AND ANTINEOPLASTIC AGENT ON THE IN VITRO GROWTH OF PB CFU-GM FROM NORMAL INDIVIDUALS AND HL-60 LEUKEMIA CELLS

  • 摘要: 采用体外微量克隆培养体系研究了组胺H2受体激动剂4-甲基组胺(4-MH)和拮抗剂雷尼替叮(ranitidine)及抗癌药阿糖胞苷分别对正常人外周血粒-巨噬系祖细胞(PBCFU-GM)和HL-60白血病细胞生长的作用。当4-MH的浓度为10-9~10-6mol·L-1时,可促进PBCFU-GM的增殖,4-MH的浓度增加至10-4mol·L-1时则表现为抑制PBCFU-GM的增殖。Ranitidine的浓度为10-9~10-5mol·L-1时,表现出对PBCFU-GM增殖的抑制作用,但在10-6mol·L-1剂量时对PBCFU-GM的抑制率低于50%,而在该剂量时对HL-60白血病细胞的抑制率已达100%,具有一定的选择性。抗癌药阿糖胞苷(Ara-C)对HL-60白血病细胞的抑制作用比对PBCFU-GM的抑制作用较强,但两者的IC50值处于同一个数量级。在强化化疗剂量10-5mol·L-1时,Ara-C对HL-60白血病细胞和PBCFU-GM正常造血祖细胞的抑制率均达100%。

     

    Abstract: Colony forming unit of granulocytes and macrophages from peripheral bloed(PBCFU-GM)represents stem and/or progenitor cells from human blood,In this paper,the effects ofhistamine H2 receptor agonist 4-methylhistamine(4-MH)and its antagonist ranitidine(Ranit) on thegrowth of PB CFU-GM cultured in methylcellulose system were studied and their differential effects onnormal PB CFU-GM and leukemic HL-60 cells were compared with the effect of the antineoplasticagent cytosine arabinoside(Ara-C). It was found that the histamine H2 receptor agonist 4-MHstimulated the growth of PB CFU-GM when 4-MH was added at the concentrations from 10-9mol·L-1 to 10-6 mol·L-1 among which the dose 10-8 mol·L-1 exerted most potent stimulatingeffect(the PB CFU-GM colony numbers was 137.68%±8. 20%、vs the control,P<0. 01).Incontrast, the antagonist Ranit showed inhibitory effect on the growth of PB CFU-GM when at theconcentrations 10-9~10-5 mol·L-1 cultured for 14d in the same methylcellulose system, Theinhibition 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, Ranitexerted much greater inhibition on HL-60 leukemic cells than on normal PB CFU-GM at the dose of10-6mol·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 CFL-GM was 100% at the intensivechemotherapeutic dose of 10-5 mol·L-1. It would appear that the histamine H2 receptor agonist 4-MH possesses stimuiating effect on thegrowth of PB CFU-GM similar to its effect on CFU-GM frorn bone marrow as documented before,Itis suggested that the histamine H2 receptor antagonist Ranit has,to some extent,potential in thetreatment of myeloid leukemia,especially when combined with antineoplastic agent Ara -C atsuboptimal doses.

     

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