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Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway

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Abstract

Dihydroartemisinin (DHA) is a semi-synthetic derivative of artemisinin, a well-tolerated and effective drug for malaria treatment, and has recently been shown to have antitumorigenic activity. However, the mechanistic basis of these activities in gliomas is unknown. The objective of this study was to evaluate whether DHA inhibits cell proliferation and invasion in glioma cells, and to elucidate the underlying mechanisms. The results demonstrate that DHA treatment significantly inhibited cell proliferation, migration and invasion, as determined using viability, transwell migration, and matrix penetration assays, respectively. Western blot analysis revealed that protein expression levels of a disintegrin and metalloproteinase 17 (ADAM17), and phosphorylated epidermal growth factor receptor and AKT (p-EGFR and p-AKT, respectively), were suppressed by DHA. EGFR and AKT phosphorylation was enhanced by stimulation with the ADAM17 agonist chemokine phorbol myristate acetate. These data suggest that DHA inhibits glioma proliferation and invasion through suppression of ADAM17 and downregulation of EGFR-PI3 K-AKT signaling.

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Acknowledgments

This work was supported by grants from the funds for Youth scientific research support program of Fujian Province Hygienic Bureau (No. 2013-2-49) to Professor Xiangrong Chen and Fujian Province Natural Science Foundation to Professor Weipeng Hu (No. 2014J01408).

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Authors and Affiliations

  1. Department of Neurosurgery, The Second Affiliated Hospital, Fujian Medical University, 34# Zhongshan Road, Quanzhou, 362000, Fujian Province, China

    Junyan Chen, Xiangrong Chen, Fan Wang, Hongzhi Gao & Weipeng Hu

  2. Department of Neurosurgery, The Jinjiang City Hospital, Quanzhou, 362000, Fujian Province, China

    Junyan Chen

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  1. Junyan Chen
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  2. Xiangrong Chen
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  3. Fan Wang
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  4. Hongzhi Gao
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Correspondence to Xiangrong Chen or Weipeng Hu.

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Chen, J., Chen, X., Wang, F. et al. Dihydroartemisinin suppresses glioma proliferation and invasion via inhibition of the ADAM17 pathway. Neurol Sci 36, 435–440 (2015). https://doi.org/10.1007/s10072-014-1963-6

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  • DOI: https://doi.org/10.1007/s10072-014-1963-6

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