| BACKGROUNDThe type I insulin-like growth factor receptor (IGF-IR) is a member of a receptor-tyrosine kinase family. Activation of the receptor triggers, through docking and phosphorylation of signal transduction molecules, the initiation of intracellular events that primarily result in proliferation, transformation and inhibition of apoptosis. It has recently reported that IGF-IR was overexpressed in a variety of human malignancies. In this experiment, we used flow cytometry (FCM) to detect the expression of IGF-IR in bone marrow leukemia cells and HL-60 cells, and used IGF-IR selective small molecule tyrosine kinase inhibitor NVP-ADW742 to block the IGF-IR pathway. The object is to investigate the correlation between the expression levels of IGF-IR in acute myeloid leukemia (AML) and its role as a target in AML therapy.METHODSIn the experiment, we used flow cytometry to analyze the expression levels of IGF-IR in bone marrow cells from 25 patients with AML and HL-60 cells. CCK-8 assay was used to determine the anti-proliferation effects of IGF-IR selective small molecule tyrosine kinase inhibitor NVP-ADW742. Apoptosis percentage and cell cycle were estimated by flow cytometry. RESULTSIGF-IR was generally expressed in AML cells and HL-60 cell line. The expression level of IGF-IR in AML marrow showed positive correlation with blast rate. NVP-ADW742 at the concentration of 0.5～5uM significantly inhibited the growth of HL-60 cells in time- and dose-dependent manner. Moreover, NVP-ADW742 also induced apoptosis of HL-60 cells in a dose-dependent manner but did not influence cell cycle significantly.CONCLUTIONIGF-IR was generally expressed in AML. It seemed that the over expression of IGF-IR might suggest malignant transformation of cells and closely related to the growth of leukemia cells. NVP-ADW742 could inhibit the proliferation and induce apoptosis of HL-60 cells in a dose-dependent manner. IGF-IR seemed a promising target in the therapy of AML.
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