Targeting Mediator Kinase Cyclin-Dependent Kinases 8/19 Potentiates Chemotherapeutic Responses, Reverses Tumor Growth, and Prolongs Survival from Ovarian Clear Cell Carcinoma
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Lines, Culture Conditions, and Reagents
2.2. Cell Proliferation and IC 50 Assays
2.3. Tissue Specimen Collection
2.4. Immunoblotting
2.5. Immunohistochemistry (IHC), H&E Staining, Immunofluorescence (If) Labeling, and Analysis
2.6. CDK8/19 CRISPR Knock-Out Generation
2.7. Public Data Mining
2.8. Mouse Xenograft Models
2.9. Animal Bioluminescent Imaging (BLI)
2.10. Anesthesia
2.11. Statistical Analyses
3. Results
3.1. CDK8/19 Is Significantly Expressed in Both Primary and Metastatic Clear Cell Ovarian Carcinoma and Correlates with Poor Prognosis
3.2. Targeting CDK8/19 Kinase Activity Is Not Independently Cytotoxic to Ovarian Cancer Cell Lines
3.3. CDK8 Inhibition Potentiates Cytotoxicity Towards Traditional Chemotherapeutics
3.4. CDK8/19 Inhibition Suppresses In Vivo Tumor Growth and Prolongs Overall Survival from Ovarian Clear Cell Carcinoma
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CDK | Cyclin-dependent kinase |
OC | Ovarian cancer |
OCCC | Ovarian clear cell carcinoma |
CCNC | Cyclin-C |
CDK8/19i | CDK8/19 inhibitor |
CDK8/19is | CDK8/19 inhibitors |
dKO | Double knock-out |
IC50 | Inhibitory concentration 50 |
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Cell Line | Initial Cell Density (Cell/Well) |
---|---|
ES-2 Luc | 2000 |
TOV-21-G | 2000 |
RMG-1 | 2500 |
SKOV-3 | 1500 |
SKOV-3 CDK 8/19 KO | 1500 |
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Barton, W.C.; Kumari, A.; Mack, Z.T.; Schools, G.P.; Quintero, L.M.; Choi, A.S.; Rangavajhula, K.; Arend, R.C.; Broude, E.V.; Mythreye, K. Targeting Mediator Kinase Cyclin-Dependent Kinases 8/19 Potentiates Chemotherapeutic Responses, Reverses Tumor Growth, and Prolongs Survival from Ovarian Clear Cell Carcinoma. Cancers 2025, 17, 941. https://doi.org/10.3390/cancers17060941
Barton WC, Kumari A, Mack ZT, Schools GP, Quintero LM, Choi AS, Rangavajhula K, Arend RC, Broude EV, Mythreye K. Targeting Mediator Kinase Cyclin-Dependent Kinases 8/19 Potentiates Chemotherapeutic Responses, Reverses Tumor Growth, and Prolongs Survival from Ovarian Clear Cell Carcinoma. Cancers. 2025; 17(6):941. https://doi.org/10.3390/cancers17060941
Chicago/Turabian StyleBarton, Wade C., Asha Kumari, Zachary T. Mack, Gary P. Schools, Liz Macias Quintero, Alex Seok Choi, Karthik Rangavajhula, Rebecca C. Arend, Eugenia V. Broude, and Karthikeyan Mythreye. 2025. "Targeting Mediator Kinase Cyclin-Dependent Kinases 8/19 Potentiates Chemotherapeutic Responses, Reverses Tumor Growth, and Prolongs Survival from Ovarian Clear Cell Carcinoma" Cancers 17, no. 6: 941. https://doi.org/10.3390/cancers17060941
APA StyleBarton, W. C., Kumari, A., Mack, Z. T., Schools, G. P., Quintero, L. M., Choi, A. S., Rangavajhula, K., Arend, R. C., Broude, E. V., & Mythreye, K. (2025). Targeting Mediator Kinase Cyclin-Dependent Kinases 8/19 Potentiates Chemotherapeutic Responses, Reverses Tumor Growth, and Prolongs Survival from Ovarian Clear Cell Carcinoma. Cancers, 17(6), 941. https://doi.org/10.3390/cancers17060941