title: Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells.
abstract: Invasion by hepatocellular carcinoma (HCC) has been reported to occur via the up-regulation of nuclear factor-kappaB (NF-κB). Sorafenib can improve the overall survival in patients with HCC, however, the association of its inhibitory mechanisms with the inactivation of NF-κB remains unclear. Here, Huh7 cell line transfected with NF-κB-luc2 vector was used to study the effects of sorafenib on NF-κB activity, on expressions of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), which were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA increased the NF-κB activity and the expressions of MMP-9 and VEGF significantly, but its effects were suppressed by sorafenib in a dose-dependent manner. Similar results were found with PD98059, an inhibitor of extracellular signal-regulated kinase (ERK). Furthermore, transfection of Huh7 cell with an inhibitor of kappaB-α mutant vector, led to reduced TPA-induced MMP-9 and VEGF mRNA expressions. Sorafenib inhibits TPA-induced MMP-9 and VEGF expressions via the suppression of ERK/NF-κB pathway in HCC cells.
authors: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, and Department of Radiation Oncology and Hospice Care Center, Mackay Memorial Hospital, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan, ROC.
authors: I-Tsang
authors: IT
authors: Chiang
authors: Yu-Chang
authors: YC
authors: Liu
authors: Wei-Hsun
authors: WH
authors: Wang
authors: Fei-Ting
authors: FT
authors: Hsu
authors: Hong-Wen
authors: HW
authors: Chen
authors: Wuu-Jyh
authors: WJ
authors: Lin
authors: Wen-Yi
authors: WY
authors: Chang
authors: Jeng-Jong
authors: JJ
authors: Hwang
mesh_terms: D001483:Base Sequence; D001557:Benzenesulfonates / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077157:Sorafenib; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001557:Benzenesulfonates; D017931:DNA Primers; D016328:NF-kappa B; D010671:Phenylurea Compounds; D011725:Pyridines; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases; D020780:Matrix Metalloproteinase 9; D013755:Tetradecanoylphorbol Acetate