The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy

  • Authors:
    • Hui Zhou
    • Jing Rao
    • Jian Lin
    • Bo Yin
    • Hansong Sheng
    • Fengchun Lin
    • Nu Zhang
    • Lin Yang
  • View Affiliations

  • Published online on: March 23, 2011     https://doi.org/10.3892/or.2011.1233
  • Pages: 1565-1571
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Abstract

Medulloblastoma is the most common malignant tumor of the central nervous system in children. The insulin-like growth factor-I receptor (IGF-IR) is an important growth factor for medulloblastoma. The novel IGF-I receptor (IGF-IR) kinase inhibitor NVP-ADW742 has in vitro activity against tumors. Daoy cells were treated with NVP-ADW742 combined with temozolomide, which is commonly used in the chemotherapy of medulloblastoma. The effects on proliferation were assayed by CCK-8 assay. Cell cycle status and apoptosis were assayed by FACS analysis. The IGF-IR signaling pathway was analyzed by RT2 Profiler™ PCR arrays and Western blotting. NVP-ADW742 inhibited IGF-IR-mediated proliferation with an IC50 of 11.12 µmol/l. The PCR array data suggested that 14 genes were down-regulated at the mRNA level after NVP-ADW742 treatment. Western blot analysis suggested that NVP-ADW742 induced early suppression of Akt, P38 and GSK-3β phosphorylation, as well as a decrease in the intracellular levels of PI3K, Akt, P38, GSK-3β and Bcl-2. Combined with NVP-ADW742 (2 µmol/l), IC50 of Daoy to temozolomide was decreased from 452.12 to 256.81 µmol/l. Cell apoptosis was enhanced from 16.18±2.47% to 23.20±2.80%. G phase arrest was also found in both the temozolomide alone group and the temozolomide combined with NVP-ADW742 group. NVP-ADW742 inhibited the activation of PI3K, Akt, P38 and GSK-3β caused by temozolomide. NVP-ADW742 enhanced the chemosensitivity of Daoy to temozolomide in vitro, as a potent anti-tumor agent highly selective against IGF-IR.

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June 2011
Volume 25 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhou H, Rao J, Lin J, Yin B, Sheng H, Lin F, Zhang N and Yang L: The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy. Oncol Rep 25: 1565-1571, 2011.
APA
Zhou, H., Rao, J., Lin, J., Yin, B., Sheng, H., Lin, F. ... Yang, L. (2011). The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy. Oncology Reports, 25, 1565-1571. https://doi.org/10.3892/or.2011.1233
MLA
Zhou, H., Rao, J., Lin, J., Yin, B., Sheng, H., Lin, F., Zhang, N., Yang, L."The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy". Oncology Reports 25.6 (2011): 1565-1571.
Chicago
Zhou, H., Rao, J., Lin, J., Yin, B., Sheng, H., Lin, F., Zhang, N., Yang, L."The insulin-like growth factor-I receptor kinase inhibitor NVP-ADW742 sensitizes medulloblastoma to the effects of chemotherapy". Oncology Reports 25, no. 6 (2011): 1565-1571. https://doi.org/10.3892/or.2011.1233