RESUMO
PKCη is involved in proliferation, differentiation, and drug resistance. However, PKCη function in EBV(+) B lymphoma remains poorly understood. Gene silencing of PKCη through siRNA knockdown inhibited cellular proliferation, induced cell cycle arrest in G0/G1 and G2/M phases, and sensitized cells to chemotherapeutic drugs. Upon PKCη knockdown, expression levels of p21, GADD45α, and TAp73 were all increased, whereas expression levels of CDK2, CDK4, CDK6, cyclin E, cyclin B1, and cdc2 were all downregulated. PKCη silencing also activated p38-MAPK, which in turn contributed to the expression of cell cycle arrest-related molecules. These results suggest that siRNA-mediated silencing of PKCη can be a potent tool to complement existing chemotherapy regimens for treating EBV(+) B lymphoma.
Assuntos
Antineoplásicos/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Herpesvirus Humano 4 , Proteína Quinase C/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Ácidos Borônicos/uso terapêutico , Bortezomib , Linfoma de Burkitt/genética , Pontos de Checagem do Ciclo Celular/genética , Proteínas de Ciclo Celular/biossíntese , Divisão Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/genética , Proteínas de Ligação a DNA/biossíntese , Humanos , Potencial da Membrana Mitocondrial , NF-kappa B/genética , Niacinamida/análogos & derivados , Niacinamida/uso terapêutico , Proteínas Nucleares/biossíntese , Compostos de Fenilureia/uso terapêutico , Fosfatidilinositol 3-Quinases/genética , Proteína Quinase C/metabolismo , Pirazinas/uso terapêutico , Interferência de RNA , RNA Interferente Pequeno/genética , Sorafenibe , Proteína Tumoral p73 , Proteínas Supressoras de Tumor/biossíntese , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/biossínteseRESUMO
Melanoma is an aggressive form of skin cancer due to its rapid metastasis. Recently, several studies have reported that selenium can prevent metastasis of melanoma cells, but the mechanism of this anti-metastatic ability is not fully understood. In this study, we investigated the effect of selenium on cell migration in melanoma and on tumor metastasis in mice. Interestingly, tumor metastasis was suppressed by selenium in a mouse model. Cell migration was measured by a wound-healing assay using selenium-treated melanoma cells. Treatment with a non-cytotoxic concentration of selenium suppressed migration of melanoma cells in a dose-dependent manner. In addition, we found decreased HIF-1α and VEGF expression in selenium-treated melanoma cells as compared to non-treated control cells. Mechanistically, our studies show that selenium inhibits IL-18 gene expression in a dose-dependent manner. IL-18 protein level was suppressed by treatment with selenium. The wound-healing assay revealed that the anti-metastatic effect of selenium was abrogated by treatment with exogenous IL-18. These results suggest that selenium might be a potent inhibitor of the metastatic capacity of melanoma cells, via down-modulation of IL-18 expression.