Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models
Abstract
:1. Introduction
2. Results
2.1. Analysis of Public Clinical Data: Expression of Downstream Target of Fingolimod and DMF Are Correlated with Better Prognostic Value in Lung Cancer Cohorts
2.2. Fingolimod and DMF Decreased NSCLC Tumor Growth In Vivo in Immunocompetent and Immunodeficient Mouse Models
2.3. Fingolimod and DMF Are Well Tolerated In Vivo
2.4. Fingolimod and DMF Differentially Affected In Vitro A549 Spheroid 3D Viability
2.5. Fingolimod and DMF Reduced In Vitro A549 Cell Growth When Cultured as 2D Monolayer
3. Discussion
4. Material and Methods
4.1. Animals
4.2. Cells and Cell Culture
4.3. 2D Cell Growth Assay
4.4. 3D Tumor Spheroid Assay
4.5. Subcutaneous Graft Animal Model
4.6. Animal Ethical Consideration and Limit Points
4.7. Treatments
4.8. Patient Survival Analysis
4.9. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DMF | Dimethyl Fumarate |
DMSO | DiMethyl SulfOxide |
EGFR | Epidermal Growth Factor |
EMT | Epithelial-to-Mesenchymal Transition |
NRF2 | Nuclear factor E2-Related Factor 2 |
OS | Overall Survival |
NSCLC | Non-Small Cell Lung Cancer |
PEG | PolyEthylene Glycol |
S1P | Sphingosine-1-Phosphate |
S1PR | Sphingosine-1-Phosphate Receptor |
SD | Standard Deviation |
TME | Tumor MicroEnvironment |
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Rupp, T.; Debasly, S.; Genest, L.; Froget, G.; Castagné, V. Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models. Int. J. Mol. Sci. 2022, 23, 8192. https://doi.org/10.3390/ijms23158192
Rupp T, Debasly S, Genest L, Froget G, Castagné V. Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models. International Journal of Molecular Sciences. 2022; 23(15):8192. https://doi.org/10.3390/ijms23158192
Chicago/Turabian StyleRupp, Tristan, Solène Debasly, Laurie Genest, Guillaume Froget, and Vincent Castagné. 2022. "Therapeutic Potential of Fingolimod and Dimethyl Fumarate in Non-Small Cell Lung Cancer Preclinical Models" International Journal of Molecular Sciences 23, no. 15: 8192. https://doi.org/10.3390/ijms23158192