High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Patient-Derived Glioblastoma Tumor Cells
2.2. Cell-Lines
2.3. Reagents and Antibodies
2.4. Image-Based High-Content Screening and Analysis
2.5. Immunoblot Assay
2.6. Cell Viability, Apoptosis Assay, and Statistics
2.7. RNA Sequencing
2.8. Kinase Assay
3. Results
3.1. Molecular and Sensitivity Testing of Glioblastoma Patient-Derived Cells to c-Met-Targeted Agents
3.2. Multi-Parametric Characterization of Glioblastoma Cells to Anti-c-Met Antibody
3.3. Identification of Abemaciclib as an Inhibitor of c-Met
3.4. Unique Role of CDK4/6 Inhibitor Abemaciclib in c-Met Regulation
3.5. Large-Scale Drug Screening Data Suggest Sensitivity Correlation of Abemaciclib and c-Met-Targeted Drugs
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Target | Drug Name | Diff. (%) | p-Value | Summary 1 |
---|---|---|---|---|
c-Met Ab | SAIT301 | −37 | 0.0004 | *** |
c-Met Inhibitor | Carbozantinib | −44.6 | <0.0001 | **** |
Crizotinib | −36.3 | 0.0007 | *** | |
Fretinib | −47.7 | <0.0001 | **** | |
Capmatinib | −49 | <0.0001 | **** | |
CDK4/6 Inhibitor | Abemaciclib | −31.9 | 0.0035 | ** |
Palbociclib | 10.7 | 0.7588 | ns 2 | |
Ribociclib | 34.1 | 0.0016 | ns |
Target | Drug Name | Z’ factor | Summary 1 |
---|---|---|---|
c-Met Ab | SAIT301 | 0.35 | * |
c-Met Inhibitor | Carbozantinib | 0.97 | ** |
Crizotinib | 0.67 | ** | |
Fretinib | 0.75 | ** | |
Capmatinib | 0.12 | * | |
CDK4/6 Inhibitor | Abemaciclib | 0.59 | ** |
Palbociclib | −0.34 | ns 2 | |
Ribociclib | −2.54 | ns |
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Oh, J.-W.; Oh, Y.J.; Han, S.; Her, N.-G.; Nam, D.-H. High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma. Cancers 2021, 13, 372. https://doi.org/10.3390/cancers13030372
Oh J-W, Oh YJ, Han S, Her N-G, Nam D-H. High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma. Cancers. 2021; 13(3):372. https://doi.org/10.3390/cancers13030372
Chicago/Turabian StyleOh, Jeong-Woo, Yun Jeong Oh, Suji Han, Nam-Gu Her, and Do-Hyun Nam. 2021. "High-Content Analysis-Based Sensitivity Prediction and Novel Therapeutics Screening for c-Met-Addicted Glioblastoma" Cancers 13, no. 3: 372. https://doi.org/10.3390/cancers13030372