Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Abemaciclib Induces G1 Arrest and Decreases Cell Growth in Metastatic Uveal Melanoma Cells
2.2. RB Protein Is Phosphorylated in Metastatic Uveal Melanoma Tissues and Abemaciclib Inhibits the Phosphorylation of RB in Metastatic UM Explants Obtained from Patients
2.3. HGF Reduces the Growth-Inhibitory Effect of Abemaciclib in Metastatic Uveal Melanoma Cells
2.4. Merestinib Overcomes HGF-Mediated Resistance to Abemaciclib in Metastatic Uveal Melanoma Cells
2.5. Merestinib Inhibits the HGF-Mediated Protection from Cellular Senescence in Abemaciclib-Treated Uveal Melanoma Cells
2.6. Abemaciclib in Combination with Merestinib Inhibits Metastatic Uveal Melanoma Tumor Growth in NSG-hHGFki Mice
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Cell Lines
4.3. Short-Interfering RNA and Transfection
4.4. MTS Assays
4.5. Cell Growth Assays
4.6. Cell-Cycle Analysis
4.7. Protein Extraction and Western Immunoblotting
4.8. Senescence Assay
4.9. Xenograft Therapeutic Trials
4.10. Immunohistochemistry
4.11. Patient Tissue Samples
4.12. Ex Vivo UM Explants
4.13. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Ohara, M.; Saito, K.; Kageyama, K.; Terai, M.; Cheng, H.; Aplin, A.E.; Sato, T. Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma. Cancers 2021, 13, 1104. https://doi.org/10.3390/cancers13051104
Ohara M, Saito K, Kageyama K, Terai M, Cheng H, Aplin AE, Sato T. Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma. Cancers. 2021; 13(5):1104. https://doi.org/10.3390/cancers13051104
Chicago/Turabian StyleOhara, Masahiro, Kengo Saito, Ken Kageyama, Mizue Terai, Hanyin Cheng, Andrew E. Aplin, and Takami Sato. 2021. "Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma" Cancers 13, no. 5: 1104. https://doi.org/10.3390/cancers13051104
APA StyleOhara, M., Saito, K., Kageyama, K., Terai, M., Cheng, H., Aplin, A. E., & Sato, T. (2021). Dual Targeting of CDK4/6 and cMET in Metastatic Uveal Melanoma. Cancers, 13(5), 1104. https://doi.org/10.3390/cancers13051104