胰岛素样生长因子Ⅰ型受体在急性髓细胞性白血病中的表达及意义  

The Expression and Significance of Type-I Insulin-like Growth Factor Receptor in the Acute Myeloid Leukemia

作　　者：孙思[1] 刘隽[1] 周咏明[1] 熊芳[1] 李玥莹[1] 刘伟[1] 王萍[1] 黄士昂[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院干细胞研究与应用中心,武汉430022

出　　处：《华中科技大学学报（医学版）》2007年第5期589-592,共4页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家杰出青年科学基金资助项目(No30225038)

摘　　要：目的研究胰岛素样生长因子Ⅰ型受体(IGF-ⅠR)在急性髓细胞性白血病(AML)中的表达特点及抗IGF-ⅠR单克隆抗体对人急性早幼粒细胞白血病细胞株HL-60的作用。方法通过流式细胞仪检测白血病细胞和HL-60细胞表面IGF-ⅠR的表达,并用鼠抗人IGF-ⅠR单克隆抗体(IGF-ⅠRMAb)作用于HL-60细胞,用CCK-8法检测细胞增殖,用流式细胞术检测细胞凋亡和细胞周期的变化。结果IGF-ⅠR在急性髓细胞白血病和HL-60细胞普遍表达,原始细胞比例越高,IGF-ⅠR表达越强(P<0.01)。0.001～10.000μg/ml的IGF-ⅠRMAb可抑制HL-60细胞生长,且随时间的延长和药物剂量的增大,这种抑制作用更加明显(P<0.05)。0.001～10.000μg/ml浓度范围内,IGF-ⅠRMAb诱导HL-60细胞的凋亡率随药物浓度的增大而增高,但对HL-60细胞周期无显著影响。结论IGF-ⅠR在急性髓细胞性白血病中普遍表达,IGF-ⅠR的高表达可能与细胞的恶性转化和白血病细胞的生长有密切关系。IGF系统对肿瘤细胞的促增殖及抗凋亡作用能被IGF-ⅠR单克隆抗体所阻断,IGF-ⅠR有可能成为抗白血病治疗的靶点。Objective To investigate the expression characteristic of type-I insulin-like growth factor receptor（IGF-ⅠR） in the acute myeloid leukemia（AML） and the effect of IGF-ⅠR monoclonal antibody（IGF-ⅠR MAb） on the biological behaviors of HL-60 cell lines.Methods The expression levels of IGF-ⅠR in bone marrow cells from 30 patients with acute myeloid leukemia and HL-60 cells were detected by flow cytometry（FCM）.CCK-8 assay was used to determine the anti-proliferative effects of IGF-ⅠR MAb.Apoptosis and cell cycle were measured by FCM.Results IGF-ⅠR was generally expressed in AML cells and HL-60 cell line.The expression level of IGF-ⅠR in AML bone marrow had a positive correlation with blast rate.IGF-ⅠR MAb at the concentration of 0.001-10.000 μg/ml significantly inhibited the growth of HL-60 cells in a time-and dose-dependent manner.Moreover,IGF-ⅠR MAb also induced apoptosis of HL-60 cells in a dose-dependent manner but didn＇t influence cell cycle significantly.Conclusion IGF-ⅠR is generally expressed in AML.It seems that the over-expression of IGF-ⅠR may suggest malignant transformation of cells and is closely related to the growth of leukemia cells.MAb inhibits the proliferation and induces apoptosis of HL-60 cells in a dose-dependent manner.IGF-ⅠR seems a promising target in the therapy of AML.

关 键 词：胰岛素样生长因子Ⅰ型受体 急性白血病 抗体 流式细胞术 

分 类 号：R733.712[医药卫生—肿瘤]