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Br J Cancer ; 117(5): 656-665, 2017 Aug 22.
Article in English | MEDLINE | ID: mdl-28751755

ABSTRACT

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.


Subject(s)
Biomarkers, Tumor/antagonists & inhibitors , Biomarkers, Tumor/genetics , Melanoma/genetics , RNA, Messenger/metabolism , Sertraline/pharmacology , Skin Neoplasms/drug therapy , Animals , Antineoplastic Agents, Alkylating/therapeutic use , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/genetics , Cell Survival/drug effects , Dacarbazine/therapeutic use , Female , Gene Expression/drug effects , Gene Expression/genetics , Gene Silencing , Humans , Melanoma/metabolism , Melanoma, Experimental/drug therapy , Mice , Mice, Inbred C57BL , RNA, Small Interfering/genetics , Sertraline/therapeutic use , Transfection , Tumor Protein, Translationally-Controlled 1 , Tumor Stem Cell Assay , Tumor Suppressor Protein p53/metabolism
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