RESUMO
Emerging evidence indicates that methylglyoxal (MG) can inhibit tumorigenesis. Glyoxalase I (GLOI), a MG degradation enzyme, is implicated in the progression of human malignancies. However, little is known about the roles of MG and GLOI in breast cancer. Our purpose was to investigate the anticancer effects of MG and inhibition of GLOI on breast cancer cells and the underlying mechanisms of these effects. Our findings demonstrate that cell viability, migration, invasion, colony formation, and tubule formation were significantly restrained by addition of MG or inhibition of GLOI, while apoptosis was significantly increased. Furthermore, the expression of p-JNK, p-ERK, and p-p38 was markedly upregulated by addition of MG or inhibition of GLOI, whereas MMP-9 and Bcl-2 expression levels were dramatically decreased. These effects were augmented by combined treatment with MG and inhibition of GLOI. Collectively, these data indicate that MG or inhibition of GLOI induces anticancer effects in breast cancer cells and that these effects are potentiated by combination of the 2. These effects were modulated by activation of the MAPK family and downregulation of Bcl-2 and MMP-9. These findings may provide a new approach for the treatment of breast cancer.
Assuntos
Neoplasias da Mama/tratamento farmacológico , Lactoilglutationa Liase/genética , Metaloproteinase 9 da Matriz/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Aldeído Pirúvico/administração & dosagem , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lactoilglutationa Liase/antagonistas & inibidores , Lactoilglutationa Liase/biossíntese , Células MCF-7 , Metaloproteinase 9 da Matriz/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Invasividade Neoplásica/genética , Proteínas Proto-Oncogênicas c-bcl-2/genéticaRESUMO
To detect cadmium ions, we constructed a specific microbial sensor and screened detecting cassettes and different fluorescence proteins. Blue fluorescence protein mTagBFP2 was selected as a reporter and a double-promoters model was used in the construction of the fusion reporter vector Pmer::merR-m-Pmer::mTagBFP2-pMD19-T. The reporter vector was then transformed into Escherichia coli MC4100 wild type strain. The medium, incubation time, initial density for induction, and the optimal detection range were determined. The specificity of the biosensor was also checked. The biosensor responded specifically to cadmium irons with low background, and the linear concentration range detection ranged from 0.1 to 75 µmol/L at the initial OD600 = 0.1 with 2 h incubation in IHMM medium. Thus we successfully constructed a specific biosensor to detect cadmium irons and provided useful strategies for development and optimization of microbial sensors to detect heavy metals.
