Adenovirus-mediated transfer of siRNA against MMP-2 mRNA results in impaired invasion and tumor-induced angiogenesis, induces apoptosis in vitro and inhibits tumor growth in vivo in glioblastoma

摘要: Invasive tumors, including gliomas, utilize proteinases to degrade extracellular matrix components and diffuse into the adjacent tissues or migrate toward distant ones. In addition, proteinase activity is required for formation of new blood vessels within tumor. Levels metalloproteinase-2 (MMP-2) are highly increased in gliomas. this study, we examined effect downregulation MMP-2 via adenovirus-mediated siRNA Here, show that delivery significantly decreased levels glioblastoma cell lines U-87 U-251. U-251 cells showed impaired invasion through matrigel as well migration from tumor spheroids transfected with adenoviral vector expressing against MMP-2. Additionally, tumor-induced angiogenesis was vitro experiments cultured human microvascular endothelial (HMECs) serum-free conditioned medium these constructs co-cultures glioma HMECs. We also observed vivo dorsal skin-fold chamber model. Moreover, inhibition induced apoptotic death vitro, suppressed growth preestablished intracranial xenografts nude mice. Thus, specific targeting may provide a novel, efficient approach treatment gliomas improve poor outcomes patients brain tumors.