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The Insulin-Like Growth factor-1 Receptor Kinase Inhibitor, NVP-ADW742, Suppresses Survival and Resistance to Chemotherapy in Acute Myeloid Leukemia Cells

The Insulin-Like Growth factor-1 Receptor Kinase Inhibitor, NVP-ADW742, Suppresses Survival and Resistance to Chemotherapy in Acute Myeloid Leukemia Cells

Yanli He, Jiahua Zhang, Jine Zheng, Wen Du, Hong Xiao, Wei Liu, Xiaoqing Li, Xiangjun Chen, Lin Yang, Shiang Huang

Oncol Res. 2010;19(1):35-43.

PMID: 21141739

Abstract:

Deregulation of insulin-like growth factor-1 receptor (IGF-1R) is closely associated with malignant transformation and tumor cell survival in various cancers. We found that IGF-1R expression level in leukemia cells positively correlated with the percentage of blast in bone marrow from de novo acute myeloid leukemia (AML) patients. Moreover, we showed that NVP-ADW742, a novel small weight molecular inhibitor of IGF-IR, could induce apoptosis in both HL-60 cell line and primary AML blasts. However, no significant alteration of cell cycle was observed in HL-60 cells. Further studies revealed that NVP-ADW742 induced Akt dephosphorylation, which might subsequently induce p38 phosphorylation and decrease antiapoptotic protein Bcl-2 expression in HL-60 cells. Finally, we demonstrated that NVP-ADW742 could synergize with Ara-C to induce the kill in a subset of drug-resistant AML specimens. We suggested that IGF-lR targeting might be therapeutically beneficial for some AML patients.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP475488234	NVP-ADW742		475488-23-4	Price

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