NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression
Abstract
:1. Introduction
2. Results
2.1. In Vitro Results
2.1.1. BAY-117082 Reduced OSCC Cell Viability
2.1.2. BAY-117082 Reduced NLRP3 Inflammasome Pathway Activation
2.1.3. BAY-117082 Modulated Apoptosis Pathway
2.2. In Vivo Results
2.2.1. BAY-117082 Reduced Tumor Growth
2.2.2. BAY-117082 Reduced NLRP3 Inflammasome Activation in CAL27 Xenograft Model
2.2.3. BAY-117082 Modulated NF-κB/IκB-α Pathway in CAL27 Xenograft Model
2.2.4. BAY-117082 Modulated CD4, CD8, and CD30 Expression in CAL27 Xenograft Model
2.2.5. BAY-117082 Modulated Apoptosis in CAL27 Xenograft Model
2.2.6. BAY-117082 Reduced Ki-67 Expression in CAL27 Xenograft Model
3. Discussion
4. Material and Methods
4.1. In Vitro Studies
4.1.1. Cell Culture
4.1.2. MTT Assay
Experimental Groups
- Control group (Ctr): Human OSCC cell lines CAL27, HSC-2, and SCC-4
- BAY-117082 0.1 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 0.1 μM for 24 h
- BAY-117082 0.5 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 0.5 μM for 24 h
- BAY-117082 1 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 1 μM for 24 h
- BAY-117082 3 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 3 μM for 24 h
- BAY-117082 5 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 5 μM for 24 h
- BAY-117082 10 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 10 μM for 24 h
- BAY-117082 30 μM group: CAL27, HSC-2, and SCC-4 cells treated with BAY-117082 30 μM for 24 h
4.1.3. Western Blot Analysis of NLRP3, ASC, Caspase-1, IL-1β, IL-18, Bax, Bcl2, and Bad
4.1.4. Immunofluorescence Assay for p53 and Caspase-1
4.2. In Vivo Studies
4.2.1. Animals
4.2.2. Xenograft Tumor Model
Experimental Groups
- Control group (vehicle): weekly intravenous (IV) administration of saline
- Control group + BAY-117082 2.5 mg/kg: intraperitoneal administration of BAY-117082 2.5 mg/kg dissolved in PBS
- Control group + BAY-117082 5 mg/kg: intraperitoneal administration of BAY-117082 5 mg/kg dissolved in PBS
4.2.3. Histological Evaluation
4.2.4. Immunohistochemical Localization of IL-1β, Ki-67, CD4, CD8, and CD30
4.2.5. Western Blot Analysis of NLRP3, ASC, Caspase-1, NF-κB, IκB-α, Bax, Bcl2, and Bcl-xL
4.3. Materials
4.4. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Scuderi, S.A.; Casili, G.; Basilotta, R.; Lanza, M.; Filippone, A.; Raciti, G.; Puliafito, I.; Colarossi, L.; Esposito, E.; Paterniti, I. NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression. Int. J. Mol. Sci. 2021, 22, 11108. https://doi.org/10.3390/ijms222011108
Scuderi SA, Casili G, Basilotta R, Lanza M, Filippone A, Raciti G, Puliafito I, Colarossi L, Esposito E, Paterniti I. NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression. International Journal of Molecular Sciences. 2021; 22(20):11108. https://doi.org/10.3390/ijms222011108
Chicago/Turabian StyleScuderi, Sarah Adriana, Giovanna Casili, Rossella Basilotta, Marika Lanza, Alessia Filippone, Gabriele Raciti, Ivana Puliafito, Lorenzo Colarossi, Emanuela Esposito, and Irene Paterniti. 2021. "NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression" International Journal of Molecular Sciences 22, no. 20: 11108. https://doi.org/10.3390/ijms222011108