Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Line and Culture Conditions
2.2. Drugs
2.3. Drug Treatment and Cell Proliferation Assay
2.4. Apoptosis
2.5. Viability Assay for Dose-Response Curve and IC50 Calculations
2.6. In Vivo Assay
2.7. Western Blots
2.8. Quantitative Real-Time PCR-Based Copy Number Assay
2.9. Quantitative Real-Time PCR Based Expression Assay
2.10. RNA Sequencing
3. Results
3.1. Improved Efficacy Using LY2874455
3.2. The Response to FGFR Inhibition in FRS2-Amplified Cell Lines Is Variable
3.3. LY2874455 Induces Long-Lasting Growth Inhibition
3.4. Both FGFR Inhibitors Inactivate MEK/ERK-Dependent Signaling in FRS2-Amplified Cells
3.5. The Expression of FGF Receptors Varies in FRS2-Amplified LPS Lines
3.6. LY2874455 Inhibits Tumor Growth In Vivo
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Hanes, R.; Munthe, E.; Grad, I.; Han, J.; Karlsen, I.; McCormack, E.; Meza-Zepeda, L.A.; Stratford, E.W.; Myklebost, O. Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma. Cells 2019, 8, 189. https://doi.org/10.3390/cells8020189
Hanes R, Munthe E, Grad I, Han J, Karlsen I, McCormack E, Meza-Zepeda LA, Stratford EW, Myklebost O. Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma. Cells. 2019; 8(2):189. https://doi.org/10.3390/cells8020189
Chicago/Turabian StyleHanes, Robert, Else Munthe, Iwona Grad, Jianhua Han, Ida Karlsen, Emmet McCormack, Leonardo A. Meza-Zepeda, Eva Wessel Stratford, and Ola Myklebost. 2019. "Preclinical Evaluation of the Pan-FGFR Inhibitor LY2874455 in FRS2-Amplified Liposarcoma" Cells 8, no. 2: 189. https://doi.org/10.3390/cells8020189