RESUMO
The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy-3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-κB activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.
Assuntos
Regulação Enzimológica da Expressão Gênica , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Tirosina Fosfatases/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Carcinógenos/farmacologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Humanos , Indóis/farmacologia , Células MCF-7 , Metaloproteinase 9 da Matriz/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteínas Tirosina Fosfatases/antagonistas & inibidores , Acetato de Tetradecanoilforbol/farmacologia , Fator de Transcrição AP-1/metabolismoRESUMO
Lipopolysaccharide (LPS), found in the outer membrane of Gram negative bacteria, only exerts its toxic effects when in free form. LPS has three major parts, lipid A, the toxic component, along with a core polysaccharide and O-specific polysaccharide. LPS monomers are known to have molecular masses between 10 to 30 kDa. Under physiological conditions, LPS exists in equilibrium between monomer and vesicle forms. LPS removal by 100 kDa ultrafiltration was more efficient (99.6% of LPS removed) with a low concentration of protein (2.0 mg/ml) compared to a high concentration (20.1 mg/ml). In the presence of different detergents (0.5% Tween 20, 1.0% taurodeoxycholate and 1.0% Triton X-100), LPS removal was more efficient at low protein concentrations (2.0 mg/ml) compared to high protein concentrations (20.1 mg/ml).