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.
Highlights
Gliomas, the most common primary malignant tumors in the central nervous system, are refractory to the surgical therapy of extensive resection and are easy to be recurrent due to their highly invasive and infiltrative growth pattern [1]
Afterwards, we examined the effects of artemether combining with short hairpin RNAs (shRNA) interference of Vascular cell adhesion molecule-1 (VCAM-1) on the cell migration, invasion, the expressions of matrix metalloproteinase-2 (MMP-2)/9, phosphorylated Akt (p-Akt) and cell apoptosis, aiming at providing novel experimental evidence for the treatment of human brain glioma
We investigated the alteration of phosphorylated Akt (p-Akt) under the pre-treatments of artemether, shRNA-VCAM-1 and artemether+shRNA-VCAM-1
Summary
The most common primary malignant tumors in the central nervous system, are refractory to the surgical therapy of extensive resection and are easy to be recurrent due to their highly invasive and infiltrative growth pattern [1]. The median survival after surgical resection alone is 6 months and only 7.5% of patients survived two years post-operatively [2]. Their biological characteristics are highly malignant, featuring strong proliferation, rapid migration, intensive invasion and a very poor prognosis. It is absolutely important to develop new agents and therapies to prevent the proliferation, migration and invasion of gliomas. Under such background, the Chinese traditional medicine might bring new hope. Agents extracted from Chines traditional medicine have been reported to have therapeutic effects against gliomas. Shao et al reported that nanoparticles loaded with Curcumina, yellow pigment in the spice turmeric displayed pro-apoptosis effect against C6 cells [7]
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