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.
出处
《湖南医科大学学报》
CSCD
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)
关键词
白血病
HL-60细胞
组胺H2受体
阿糖胞苷
methylhistamine
Ara C
HL 60 leukemia cell
cell proliferation
drug effects
