The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, suppresses survival and resistance to chemotherapy in acute myeloid leukemia cells
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He, Yanli, Zhang, Jiahua, Zheng, Jin'e, Du, Wen, Liu, Wei, Li, Xiaoqing, Chen, Xiangjun, Xiao, Hong, Yang, Lin, Huang, Shiang and Jeay, Sebastien (2010) The insulin-like growth factor-I receptor kinase inhibitor, NVP-ADW742, suppresses survival and resistance to chemotherapy in acute myeloid leukemia cells. Oncology Research, 19 (1). pp. 35-43. ISSN 0965-0407
Abstract
The overexpression of Insulin-like growth factor-I receptor (IGF-IR) is strongly suggested to exert a role in malignant transformation and survival promotion in solid tumors such as breast cancer and prostate cancer, while fewer studies investigated the pathophysiological role of Insulin-like growth factor-I (IGF-I) signaling in acute myeloid leukemia (AML). In this study, we firstly found that the IGF-IR expression level positively correlated with the blast counts in de novo AML patients. Moreover, we observered that inhibitor of IGF-IR by NVP-ADW742, a novel kinase inhibitor of IGF-IR, could induce apoptosis in both HL-60 cell line and primary AML blasts, However, no significant alteration in the cell cycle status was observed in HL-60 cells. Further studies showed that NVP-ADW742 induced Akt dephosphorylation and p38 phosphorylation, decreased the expression of anti-apoptotic protein bcl-2 in HL-60 cells. Besides, we also demostrated that NVP-ADW742 could synergize with ara-C to induce apoptosis in subsets primary drug-resistant AML blasts. Therefore, IGF-IR targeting might be of therapeutic benefit for some AML patients.
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| Additional Information: | author cannot archive pre-print (ie pre-refereeing |
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| Date Deposited: | 13 Oct 2015 13:16 |
| Last Modified: | 13 Oct 2015 13:16 |
| URI: | https://oak.novartis.com/id/eprint/2572 |