Serine and matrix metalloproteinase inhibition for malignant astrocytoma therapy.

点击翻译按钮获取中文摘要

In this study, we investigated that the role of NF-kB for regulation of the expression of urokinase-type plasminogen activator (uPA) and signal transduction in tumor necrosis factor-α (TNF-α)-induced cytotoxicity. We found that NF-kB (p50 and p65 subunits) is activated in human astrocytomas in vivo and in vitro, which contributed the overexpression of uPA.Activation of nuclear factor-κB (NF-κB) protects against TNF-α-induced apoptosis in human glioblastoma cells in vitro. The results of zymography and in vitro invasion assay showed that NF-kB inhibitors (steroid, aspirin and pentoxyfiline) suppressed the expression of uPA and invasiveness of human glioblastoma cells in vitro. This effect was accelerated by BB-94, gelatinase inhibitor. Combined with NF-kB inhibitors and recombinant human TNF-alpha, the invasive potential of human glioblastoma cells decreased and induced apoptosis in glioblastoma cells. Our results suggest that the constitutive activation of NF-κB subunits in malignant astrocytoma is realistic traget for malignant astrocytomas therapy modifying the serine and matrix metalloproteinase activities.