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      Artemether Combined with shRNA Interference of Vascular Cell Adhesion Molecule-1 Significantly Inhibited the Malignant Biological Behavior of Human Glioma Cells

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          Abstract

          Artemether is the derivative extracted from Chinese traditional herb and originally used for malaria. Artemether also has potential therapeutic effects against tumors. Vascular cell adhesion molecule-1 (VCAM-1) is an important cell surface adhesion molecule associated with malignancy of gliomas. In this work, we investigated the role and mechanism of artemether combined with shRNA interference of VCAM-1 (shRNA-VCAM-1) on the migration, invasion and apoptosis of glioma cells. U87 human glioma cells were treated with artemether at various concentrations and shRNA interfering technology was employed to silence the expression of VCAM-1. Cell viability, migration, invasiveness and apoptosis were assessed with MTT, wound healing, Transwell and Annexin V-FITC/PI staining. The expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and phosphorylated Akt (p-Akt) was checked by Western blot assay. Results showed that artemether and shRNA-VCAM-1 not only significantly inhibited the migration, invasiveness and expression of MMP-2/9 and p-Akt, but also promoted the apoptosis of U87 cells. Combined treatment of both displayed the maximum inhibitory effects on the malignant biological behavior of glioma cells. Our work revealed the potential therapeutic effects of artemether and antiVCAM-1 in the treatments of gliomas.

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          Author and article information

          Contributors
          Role: Editor
          Journal
          PLoS One
          PLoS ONE
          plos
          plosone
          PLoS ONE
          Public Library of Science (San Francisco, USA )
          1932-6203
          2013
          11 April 2013
          : 8
          : 4
          : e60834
          Affiliations
          [1 ]Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People’s Republic of China
          [2 ]Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang, Liaoning Province, People’s Republic of China
          [3 ]Institute of Pathology and Pathophysiology, China Medical University, Shenyang, Liaoning Province, People’s Republic of China
          UAE University, United Arab Emirates
          Author notes

          Competing Interests: The authors have declared that no competing interests exist.

          Conceived and designed the experiments: YBW YH PW YXX YHL. Performed the experiments: YBW YH ZL YLY BY. Analyzed the data: YBW YH PW ZL BY. Contributed reagents/materials/analysis tools: YBW YH ZL YXX YLY YHL. Wrote the paper: YBW YH YXX YHL.

          Article
          PONE-D-12-38624
          10.1371/journal.pone.0060834
          3623969
          23593320
          48671a71-c55b-4912-af4b-dd7117c69a46
          Copyright @ 2013

          This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

          History
          : 5 December 2012
          : 3 March 2013
          Page count
          Pages: 14
          Funding
          This work was supported by grants from the Natural Science Foundation of China (no. 81171131, no. 81172197, no. 81272564, no. 30973079 and no. 81072056) ( www.nsfc.gov.cn), the special fund for Scientific Research of Doctor-degree Subjects in Colleges and Universities, (no. 20092104110015, 20102104110009) ( www.cutech.edu.cn), the Natural Science Foundation of Liaoning Province in China (no. 201102300) ( www.lninfo.gov.cn), Liaoning Science and Technology Plan Projects (no. 2011225020) ( www.lninfo.gov.cn), College Science and Technology Research Project of Education Department in Liaoning Province (no. L2010585) ( www.lnein.gov.cn), and Shenyang Science and Technology Plan Projects (no. F11-264-1-15 and F12-277-1-05) (http: // www.systplan.gov.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
          Categories
          Research Article
          Biology
          Molecular Cell Biology
          Signal Transduction
          Signaling Cascades
          Apoptotic Signaling Cascade
          Signaling in Cellular Processes
          Apoptotic Signaling
          Medicine
          Oncology
          Cancer Treatment
          Chemotherapy and Drug Treatment
          Cancers and Neoplasms
          Neurological Tumors
          Glioma

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          Uncategorized

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