NUMERO: #20250212

Título: NF-KB PHARMACOLOGICAL INHIBITION ENHANCES CHEMOSENSITIVITY TO CISPLATIN IN ORAL SQUAMOUS CELL CARCINOMA

Nome do Apresentador: Hélen Kaline Farias BEZERRA

Categoria do Trabalho: Painel de pesquisa científica (PPC)

Área Temática: Oncologia

Resumo: Objective: Chemoresistance in oral squamous cell carcinoma (OSCC) remains a major therapeutic challenge, with cancer stem cells (CSCs) implicated as key mediators. Given the role of NFκB in tumor survival, we investigated whether its pharmacological inhibition could target CSCs and enhance cisplatin chemosensitivity.
Study design: The NFκB inhibitor used was emetine. CSCs from OSCC were characterized through tumorspheres formation and ALDH enzymatic activity quantified by flow cytometry. Emetines IC50 was determined specifically in CSC populations. NFκB activation status was evaluated via phosphorylated p65 immunofluorescence. For chemosensitization assays, OSCC cells received emetine pretreatment (24h) followed by cisplatin at previously established IC50 concentrations.
Results: Emetine exhibited an IC50 of 0.5μM in OSCC-derived CSCs. Emetine reduced the ALDH+ population and NFκB pathway activation after a single dose of emetine. Also, OSCC cells sensitized by emetine exhibited a lowering of the cisplatin IC50 from 3.9 μM to 1.3 μM in SCC9 cells.
Conclusion: These findings confirm CSCs role in OSCC chemoresistance and demonstrate that NFκB inhibition with emetine effectively targets this population while potentiating cisplatin response by reducing dose and toxicity. This two-hit approach presents a promising therapeutic strategy for treatment-refractory OSCC.

Autor 1:  Hélen Kaline Farias BEZERRA

E-mail 1:  [email protected]

Autor 2:   Sebastião Silvério SOUSA-NETO

E-mail 2:  [email protected]

Autor 3 :  Rogerio Moraes CASTILHO

E-mail 3:  [email protected]

Autor 4:  Pablo Agustin VARGAS

E-mail 4:  [email protected]

Autor 5:  Luan César SILVA

E-mail 5:  [email protected]