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Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)

Authors :
Giovanna Casili
Sarah Adriana Scuderi
Marika Lanza
Alessia Filippone
Deborah Mannino
Raffaella Giuffrida
Cristina Colarossi
Marzia Mare
Anna Paola Capra
Federica De Gaetano
Marco Portelli
Angela Militi
Salvatore Cuzzocrea
Irene Paterniti
Emanuela Esposito
Source :
Cancers; Volume 15; Issue 10; Pages: 2796
Publication Year :
2023
Publisher :
Multidisciplinary Digital Publishing Institute, 2023.

Abstract

Oral squamous cell carcinoma (OSCC) is a commonly occurring head and neck cancer and it is characterized by a high metastasis grade. The aim of this study was to evaluate for the first time the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph node, lung, and spleen tissues. Our results demonstrated that BAY-117082 treatment, at doses of 2.5 mg/kg and 5 mg/kg, was able to significantly reduce the presence of microscopic tumor islands and nuclear pleomorphism in tongue tissues and modulate the NLRP3 inflammasome pathway activation in tongue tissues, as well as in metastatic organs such as lung and spleen. Additionally, BAY-117082 treatment modulated the epithelial–mesenchymal transition (EMT) process in tongue tissue as well as in metastatic organs such as lymph node, lung, and spleen, also reducing the expression of matrix metalloproteinases (MMPs), particularly MMP2 and MMP9, markers of cell invasion and migration. In conclusion, the obtained data demonstrated that BAY-117082 at doses of 2.5 mg/kg and 5 mg/kg were able to reduce the tongue tumor area as well as the degree of metastasis in lymph node, lung, and spleen tissues through the NLRP3 inflammasome pathway inhibition.

Details

Language :
English
ISSN :
20726694
Database :
OpenAIRE
Journal :
Cancers; Volume 15; Issue 10; Pages: 2796
Accession number :
edsair.doi.dedup.....a5024597cca7868073dec1fb3bebc383
Full Text :
https://doi.org/10.3390/cancers15102796