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

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.

Integrin α4 is involved in the regulation of glioma-induced motility of bone marrow mesenchymal stem cells

“…Therefore, it is reasonable to conclude that glioma may promote the migration of BMSCs by increasing the expression of integrin α4. Additionally, we suggest that VCAM-1 and integrin α4 might interact with their own ligands in the extracellular matrix, respectively, which promote the migration in a 2-fold effect, which is similar to tumor cells such as U87MG (27,28).…”

CRM197 in Combination With shRNA Interference of VCAM-1 Displays Enhanced Inhibitory Effects on Human Glioblastoma Cells

“…Moreover, studies have shown that anti-VCAM-1 antibody could significantly inhibit the growth of glioma and prolong the survival of tumor bearing rats (Zhan et al, 2011). Our previous work also revealed that the interference silence of VCAM-1 not only inhibited the proliferation, invasion of glioma cell but also induced apoptosis (Wang et al, 2013a). Thus anti-VCAM-1 treatment may present a potential strategy for the therapy of glioblastoma.…”

“…Thus anti-VCAM-1 treatment may present a potential strategy for the therapy of glioblastoma. Extracellular matrix (ECM) is considered to be a barrier against glioma metastasis (Wang et al, 2013a). The family of matrix metalloproteinases (MMPs), identified as the invasion related proteins, plays a key role in degrading ECM, which contributes to the metastasis and invasion of malignant tumors (Wang et al, 2013a).…”

“…Extracellular matrix (ECM) is considered to be a barrier against glioma metastasis (Wang et al, 2013a). The family of matrix metalloproteinases (MMPs), identified as the invasion related proteins, plays a key role in degrading ECM, which contributes to the metastasis and invasion of malignant tumors (Wang et al, 2013a). MMP-2 and MMP-9 are the most important ones for the malignancy of gliomas among other MMPs and are highly expressed on glioma cells (Forsyth et al, 1999).…”

“…MMP-2 and MMP-9 are the most important ones for the malignancy of gliomas among other MMPs and are highly expressed on glioma cells (Forsyth et al, 1999). We reported previously that down-regulation of VCAM-1 expression led to decreased activity of MMP-2 and 9 (Wang et al, 2013a). Phosphoinositide-3-kinase (PI3K) pathway is an important signaling pathway involved in crucial cellular processes such as proliferation, survival, motility, and angiogenesis (Scrima et al, 2012).…”