Effects of dexamethasone on Flt3 receptor expression and proliferation induced by recombinant human Flt3 ligand in malignant hematopoietic cells  

地塞米松对恶性造血细胞Flt3受体表达及重组人Flt3配体诱导的细胞增殖的影响

作　　者：许志祥[1] 徐颖[1] 朱剑昆[1] 李彩霞[1] 李颖[1] 张学光[1] 

机构地区：[1]苏州大学生命科学院医学生物技术研究所免疫研究室,苏州中国215007

出　　处：《Acta Pharmacologica Sinica》2001年第6期58-64,共7页中国药理学报（英文版）

基　　金：grant from the IAEA Foundation for Protection of Acute Irradiation Injury under Contract, No CPR/9/025

摘　　要：AIM: To investigate the effect of dexamethasone (DXM) on the expression of Flt3 receptor and the proliferation mediated by recombinant human Flt3 ligand (rhFL) in leukemia cells. METHODS: Eighteen malignant hematopoietic cell lines and 10 leukemia blasts from leukemia patients were examined by flow cytometry for the expression of Flt3 receptor before and after incubation with DXM 0. 1 μmol/L for 24 h. The effect of DXM on the proliferation of malignant hematopoietic cells was measured by MTT assay. RESULTS: (1) Expression of the Flt3 receptor in malignant hematopoietic cell lines and leukemia blasts was widespread and extremely heterogeneous; (2) The presence of receptor on the surface of malignant hematopoietic cell didn't necessarily imply a significant ligand-induced response, at least in terms of proliferation. Conversely, some Flt3 receptor-negative malignant hematopoietic cells responded to rhFL; (3) DXM down-regulated the expression of Flt3 receptor and inhibited the proliferation induced by rhFL in some malignant hematopoietic cell lines and fresh leukemia cells. CONCLUSION: DXM may down-regulate the expression of Flt3 receptor on the surface of malignant hematopoietic cells and inhibit the proliferation induced by rhFL. A combination of rhFL and DXM may serve to control hematopoietic defects in malignant hematopoietic diseases.目的:研究地塞米松(DXM)对恶性造血细胞表面Flt3受体表达及重组人Flt3配体(rhFL)介导的恶性造血细胞增殖的影响。方法:采用流式细胞仪分析18株恶性造血细胞系细胞和10例新鲜白血病原代细胞表面Flt3受体的表达,及与DXM 0.1μmol/L共育24h后Flt3受体的表达,用NTT法测定DXM对rhFL介导的恶性造血细胞增殖的影响。结果:(1)恶性造血细胞系细胞和白血病原代细胞Flt3受体的表达广泛并呈多样性。(2)恶性细胞表面Flt3受体的表达与rhFL介导的恶性细胞增殖无一定相关性,rhFL促进部分Flt3受体阴性细胞的增殖。(3)DXM下调Flt3受体的表达,抑制rhFL介导的部分恶性造血细胞系细胞和新鲜白血病原代细胞的增殖。结论:DXM可下调恶性造血细胞表面Flt3受体的表达,抑制rhFL介导的恶性造血细胞的增殖。DXM和rhFL联合应用,可使rhFL在恶性造血系统疾病的造血功能缺乏治疗时更为安全。

关 键 词：recombinant proteins recombinant human Flt3 ligand receptor protein-tyrosine kinases hematologic neoplasms DEXAMETHASONE 

分 类 号：R96[医药卫生—药理学]