RESUMO
BACKGROUND: Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels. METHODS: We evaluate the role of TCTP in melanoma using sertraline and siRNA. Cell viability, migration, and clonogenicity were assessed in human and murine melanoma cells in vitro. Sertraline was evaluated in a murine melanoma model and was compared with dacarbazine, a major chemotherapeutic agent used in melanoma treatment. RESULTS: Inhibition of TCTP levels decreases melanoma cell viability, migration, clonogenicity, and in vivo tumour growth. Human melanoma cells treated with sertraline show diminished migration properties and capacity to form colonies. Sertraline was effective in inhibiting tumour growth in a murine melanoma model; its effect was stronger when compared with dacarbazine. CONCLUSIONS: Altogether, these results indicate that sertraline could be effective against melanoma and TCTP can be a target for melanoma therapy.
Assuntos
Biomarcadores Tumorais/antagonistas & inibidores , Biomarcadores Tumorais/genética , Melanoma/genética , RNA Mensageiro/metabolismo , Sertralina/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/uso terapêutico , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Dacarbazina/uso terapêutico , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Inativação Gênica , Humanos , Melanoma/metabolismo , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética , Sertralina/uso terapêutico , Transfecção , Proteína Tumoral 1 Controlada por Tradução , Ensaio Tumoral de Célula-Tronco , Proteína Supressora de Tumor p53/metabolismoRESUMO
This study aimed to characterize meticillin-resistant Staphylococcus aureus (MRSA) lineages circulating in a Brazilian teaching hospital. MRSA isolates from nasal swabs were evaluated to assess antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec), Panton-Valentine leucocidin status, pulsed-field gel electrophoresis profile and multi-locus sequence type (MLST) analysis. Eighty-three MRSA isolates were analysed. SCCmec III (43.4%) and IV (49.4%) were predominant. ST1-IV (USA400) was more common in internal medicine (P = 0.002) whereas 'clone M' (SCCmec III) was more common in the medical and surgical intensive care unit (P = 0.004), and all isolates were ST5-IV (USA800) in dermatology (P < 0.001). These data improved the understanding of the MRSA epidemiology inside the hospital and helped to establish effective control measures.