组胺H_2受体激动剂4-甲基组胺对阿糖胞苷抑制HL-60细胞增殖的负性影响  

The negative effect of 4-methylhistamine, an H_2 receptor agonist, on cytotoxicity of Ara-C for HL-60 leukemia cells

作　　者：何群 徐有恒 

出　　处：《湖南医科大学学报》2000年第1期1-5,共5页Bulletin of Hunan Medical University

基　　金：国家自然科学基金!(39170323)

摘　　要：在用 4 甲基组胺 (4 MH)激动HL 60细胞上的组胺H2 受体后 ,观察抗白血病药物阿糖胞苷 (Ara C)对HL 60白血病细胞增殖抑制作用的影响。以3H TdR掺入和集落培养为增殖指标 ,用NBT还原试验检测细胞的分化 ,用HPLC和荧光分光光度法分别检测细胞内cAMP和Ca2 +离子的变化。结果显示 ,HL 60细胞上的组胺H2 受体经 4 MH激动后 ,Ara C对其增殖的抑制作用明显减弱 (P <0 .0 1)。 4 MH升高HL 60细胞内cAMP和Ca2 +水平 ,启动HL 60细胞分化机制 ,抑制HL 60细胞的增殖等动因与癌细胞对Ara C不敏感可能有关。Objective: To study the effect of 4 methylhistamine on cytotoxicity of Ara C for HL 60 leukemia cells in vitro. Methods: Proliferation of HL 60 cells was determined by semi solid colony culture and 3 H TdR incorporation. The typical NBT reduction was used to check cell differentiation. Intracellular cAMP and calcium concentration were determined by high pressure liquid chromatography(HPLC) and fluorescence method, respectively. Results: When HL 60 cells were pretreated with 10 -8 ?mol·L -1 4 MH for 24?hrs, the cytotoxicity of Ara C[10 -8 ～10 -4 mol·L -1 ] for HL 60 leukemia cells was significantly decreased both in liquid and semisolid culture. The result of colony counting indicated that the IC 50 for HL 60 cells were 1.68×10 -6 mol·L -1 with 4 MH pretreatment nad 2.14×10 -8 mol·L -1 without 4 MH pretreatment, respectively. Therefore, the potency of Ara C was reduced nearly 80 times according to IC 50 doses. It is interesting that 10 -6 mol·L -1 ranitidine, an antagonist of H 2 receptor, can elaborate the negative effect of 4 MH on cytotoxicity of Ara C for HL 60 cells. Conclusion: The dose of Ara C should be adequately increased, or Ara C should be used with H 2 receptor antagonist such as ranitidine when treating myeloid leukemia patients.

关 键 词：白血病 HL-60细胞 组胺H2受体 阿糖胞苷 

分 类 号：R329.28[医药卫生—人体解剖和组织胚胎学]