U0126, a mitogen-activated protein kinase kinase inhibitor, inhibits the invasion of human A375 melanoma cells
| Autor: | Xiaokang Ge, Ya Min Fu, Gary G. Meadows |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Flavonoids
Mitogen-Activated Protein Kinase Kinases MAPK/ERK pathway Cancer Research Matrigel biology Kinase Urokinase-Type Plasminogen Activator Protein kinase R Matrix Metalloproteinase 9 Oncology Mitogen-Activated Protein Kinase Kinase Inhibitor Mitogen-activated protein kinase Nitriles Butadienes Tumor Cells Cultured Cancer research biology.protein Humans Neoplasm Invasiveness Enzyme Inhibitors Phosphorylation Signal transduction Protein kinase A Melanoma |
| Zdroj: | Cancer Letters. 179:133-140 |
| ISSN: | 0304-3835 |
| DOI: | 10.1016/s0304-3835(02)00004-6 |
| Popis: | The anti-invasive ability of the mitogen-activated protein kinase (MAPK) kinase inhibitor, U0126, was examined in human A375 melanoma cells in vitro. The effect was compared to that of PD98059, another commonly used MEK (MAPK kinase) inhibitor. U0126 or PD98059 showed a dose-dependent inhibition of A375 cell invasion through growth factor-reduced Matrigel. U0126 was more potent than PD98059 in suppressing tumor cell invasion. Both compounds significantly decreased urokinase plasminogen activator (uPA) and matrix metalloproteinases-9 (MMP-9) concentrations in conditioned media. At 5 microM, U0126 inhibited phosphorylation of the MEK 1/2 to a non-detectable level within 24 h. The phosphorylation of extracellular signal-related kinase 1/2 was also dramatically suppressed by the treatment with 10 microM U0126 or 40 microM PD98059. Both compounds suppressed the protein expression of c-Jun, but not c-Fos. The expression of uPA and MMP-9 was also inhibited. Our data suggest that U0126 is an effective agent in inhibiting human A375 melanoma cell invasion and that the effect is partially due to the decreased production of uPA and MMP-9. |
| Databáze: | OpenAIRE |
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