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Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
TCTP as a therapeutic target in melanoma treatment
M Boia-Ferreira1, A B Basílio1, A E Hamasaki1
1Department of Cell Biology, Centro Politécnico, Federal University of Paraná, UFPR, Jardim das Américas, CEP 81531-990, Curitiba, Paraná, Brazil.
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.
Insights
Sertraline effectively inhibits melanoma growth by targeting Translationally Controlled Tumor Protein (TCTP). This study suggests TCTP as a potential therapeutic target for melanoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Translationally controlled tumor protein (TCTP) is an anti-apoptotic protein implicated in various cancers.
- TCTP overexpression is observed in multiple tumor types, and its silencing can induce tumor reversion.
- There is a known reciprocal repression between TCTP and P53, and sertraline has been shown to decrease TCTP levels.
Purpose of the Study:
- To investigate the role of TCTP in melanoma.
- To evaluate the efficacy of sertraline, an inhibitor of TCTP, in melanoma treatment.
- To assess TCTP as a potential therapeutic target for melanoma.
Main Methods:
- Assessed melanoma cell viability, migration, and clonogenicity in vitro using human and murine melanoma cells with TCTP inhibition via sertraline and siRNA.
- Evaluated sertraline's efficacy in a murine melanoma model.
- Compared sertraline's anti-melanoma effects with dacarbazine, a standard chemotherapy agent.
Main Results:
- Inhibition of TCTP levels significantly reduced melanoma cell viability, migration, clonogenicity, and in vivo tumor growth.
- Sertraline treatment diminished migration and colony formation in human melanoma cells.
- Sertraline demonstrated superior efficacy in inhibiting tumor growth in a murine melanoma model compared to dacarbazine.
Conclusions:
- Sertraline shows potential as an effective therapeutic agent against melanoma.
- Targeting TCTP presents a promising strategy for melanoma therapy.
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