Artemether combined with shRNA interference of vascular cell adhesion molecule-1 significantly inhibited the malignant biological behavior of human glioma cells

Ying-Bin Wang; Yi Hu; Zhen Li; Ping Wang; Yi-Xue Xue; Yi-Long Yao; Bo Yu; Yun-Hui Liu

doi:10.1371/journal.pone.0060834

Artemether combined with shRNA interference of vascular cell adhesion molecule-1 significantly inhibited the malignant biological behavior of human glioma cells

PLoS One. 2013 Apr 11;8(4):e60834. doi: 10.1371/journal.pone.0060834. Print 2013.

Authors

Ying-Bin Wang¹, Yi Hu, Zhen Li, Ping Wang, Yi-Xue Xue, Yi-Long Yao, Bo Yu, Yun-Hui Liu

Affiliation

¹ Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning Province, People's Republic of China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Annexin A5
Apoptosis / drug effects
Artemether
Artemisinins / pharmacology*
Blotting, Western
Cell Line, Tumor
Cell Movement / drug effects
Drugs, Chinese Herbal / pharmacology*
Fluorescein-5-isothiocyanate
Glioma / drug therapy*
Humans
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / metabolism
Neoplasm Invasiveness / prevention & control
RNA Interference
RNA, Small Interfering / genetics
Tetrazolium Salts
Thiazoles
Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

Annexin A5
Artemisinins
Drugs, Chinese Herbal
RNA, Small Interfering
Tetrazolium Salts
Thiazoles
Vascular Cell Adhesion Molecule-1
Artemether
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
thiazolyl blue
Fluorescein-5-isothiocyanate

Grants and 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.