| Summary: | 博士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 100 === Invasion through activation of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in hepatocellular carcinoma (HCC) were via the regulation of nuclear factor-kappaB (NF-κB). Sorafenib can improve the overall survival in patients with advanced HCC and its inhibitory mechanism associated with the inactivation of NF-κB remains unclear. Here, Huh7 cells transfected with NF-κB-luc2 vector were used to study the effects of sorafenib on NF-κB activity and expressions of MMP-9 and VEGF induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) with bioluminescent imaging, Western blotting, reverse-transcription polymerase chain reaction, electrophoretic mobility shift and gelatin zymography assays. TPA increased significantly NF-κB activity and expressions of MMP-9 and VEGF, which was suppressed by sorafenib, in a dose-dependent manner. Similar results were reproduced by using PD98059, an extracellular signal-regulated kinase (ERK) inhibitor. Furthermore, HCC cells transfected with IκBα mutant vector (p-IκBαM) exhibited decreased TPA-induced MMP-9 and VEGF mRNA expressions. Together, sorafenib inhibits TPA-induced MMP-9 and VEGF expressions via the suppression of ERK/NF-κB pathway in HCC cells.
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