GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo

Zhou,Xiang; Shen,Fazheng; Ma,Pengju; Hui,Hongyan; Pei,Sujuan; Chen,Ming; Wang,Zhongwei; Zhou,Wenke; Jin,Baozhe

doi:10.3892/mmr.2015.4129

GSK1838705A, an IGF-1R inhibitor, inhibits glioma cell proliferation and suppresses tumor growth in vivo

Authors:
- Xiang Zhou
- Fazheng Shen
- Pengju Ma
- Hongyan Hui
- Sujuan Pei
- Ming Chen
- Zhongwei Wang
- Wenke Zhou
- Baozhe Jin
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China, Department of Pharmacy, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan 453100, P.R. China
Published online on: July 28, 2015 https://doi.org/10.3892/mmr.2015.4129
Pages: 5641-5646
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Glioma is a type of primary malignant tumor of the central nervous system in humans. At present, standard treatment involves surgical resection, followed by radiation therapy and chemotherapy. However, the prognosis is poor and the long‑term survival rate remains low. An improved understanding of the molecular basis for glioma tumorigenesis is in urgently required. The pro‑survival effect of the insulin‑like growth factor (IGF) signaling pathway has been implicated in progression of the glioma disease state. GSK1838705A is a novel, small molecule kinase inhibitor of IGF‑IR, which inhibits IGF signal transduction and downstream target activation. Its anti-proliferative activity has been demonstrated in various tumor cell lines. The present study investigated the potential use of GSK1838705A for the treatment of glioma. Human U87MG glioma cells were used to examine the inhibitory activity of GSK1838705A in cell proliferation, migration and apoptosis. The antitumor activity of GSK1838705A was assessed in a xenograft mouse model. GSK1838705A inhibited the growth and induced the apoptosis of the U87MG glioma cells in a dose‑dependent manner. The GSK1838705A‑treated cells exhibited reduced migratory activity in response to chemoattractants. The present study further demonstrated the antitumor activity of GSK1838705A in vivo. The administration of GSK1838705A significantly inhibited the growth of glioma tumors by inducing the apoptosis of tumor cells. These results suggested that targeting IGF signaling with GSK1838705A may be a promising therapeutic strategy for the treatment of patients with glioma.

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