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FTY720 reduces migration and invasion of human glioblastoma cell lines via inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway

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Tumor Biology

Abstract

2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720), a synthetic compound from Isaria sinclairii, has been proven to possess various biological benefits including anti-cancer activity. However, the effects and related mechanisms of FTY720 on the migration and invasion of glioblastoma cells are still unclear. In the present study, we utilized U251MG and U87MG human glioblastoma cell lines to assess the effects of FTY720. We found that FTY720 significantly inhibited migration and invasion of glioblastoma cells. The anti-migration and invasion effects of FTY720 were associated with its down-regulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 while up-regulation of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. Furthermore, FTY720 modulated the expression of roundabouts 1 (ROBO1), Rho-associated kinase-1 (ROCK1), and epithelial-to-mesenchymal transition (EMT)-related factors. In addition, the phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) signaling pathway participated in FTY720-mediated suppression of migration and invasion. Thus, our findings demonstrated that FTY720 reduced glioblastoma cells migration and invasion via multiple signaling pathways, suggesting that FTY720 is a potential therapeutic agent against glioblastoma.

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Acknowledgments

This work was supported by Grants from the National Natural Science Foundation of China (No. 81070974 & No. 81271377), the Jiangsu Provincial Key Subject (no. X4200722), and Jinling Hospital of Nanjing, China (no. 2010Q017).

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Authors and Affiliations

  1. Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, China

    Li Zhang, Handong Wang, Jianhong Zhu, Ke Ding & Jianguo Xu

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  1. Li Zhang
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  2. Handong Wang
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  3. Jianhong Zhu
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  4. Ke Ding
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  5. Jianguo Xu
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Correspondence to Handong Wang.

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Zhang, L., Wang, H., Zhu, J. et al. FTY720 reduces migration and invasion of human glioblastoma cell lines via inhibiting the PI3K/AKT/mTOR/p70S6K signaling pathway. Tumor Biol. 35, 10707–10714 (2014). https://doi.org/10.1007/s13277-014-2386-y

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  • DOI: https://doi.org/10.1007/s13277-014-2386-y

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