Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time
Abstract
:1. Introduction
2. Materials and Methods
2.1. Therapeutic Agents
2.2. Tissue Culture
2.2.1. Establishment of Concurrent 2D and 3D Tissue Culture
2.2.2. Measurement of Spheroid Growth in 3D Culture
2.3. Cellular Assays
2.3.1. Apoptosis and Necrosis
2.3.2. Viability, Cell Proliferation, Migration and Invasion Assays
2.3.3. Observation of Colony Formation Following Treatment in 3D Culture
2.3.4. Chemoresistance
2.4. Statistical Analysis
3. Results
3.1. Spheroid Formation and Experimental Design
3.2. In Caov-3 Cells, Paclitaxel Alone Does Not Suppress 3D Ovarian Cancer Growth in an Extended Kinetic Assay, Whereas Epigenetic Therapy Causes Spheroid Shrinkage
3.3. In Ovcar-3 Cells, the Combination of Classic Chemotherapy with Epigenetic Therapy Is Most Effective
3.4. Cells Observed over an Extended Kinetic in 2D Culture Demonstrate the Same Trends Seen in 3D Culture, However, the Effect Is More Pronounced in 3D as Compared to 2D
3.5. Physiologic Changes in Ovarian Cancer Cells Following Chemotherapy or Epigenetic Treatments in 3D Culture
3.5.1. Spheroid-Derived Cells Exhibit No Change in Proliferation Following Treatment with Paclitaxel; However, There Is a Decreased Proliferative Ability Noted following Treatment with Epigenetic Therapy
3.5.2. Cells Treated with Paclitaxel Demonstrate Increased Migration Capability, Whereas Those Treated with Epigenetic Therapy Demonstrate Decreased Invasion Capability
3.5.3. Epigenetic Therapy Reduces the Ability for Ovarian Cancer Cells to Form Colonies, Whereas Classic Chemotherapy Does Not Have This Effect
3.6. Chemoresistance Observed in 3D Ovarian Cancer Cells Is Reversible with Epigenetic Therapy
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
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Treatment | Mechanism | Relevance |
---|---|---|
cisplatin | classic chemotherapy; platinum alkylating agent | commonly used in HGSC alone or in combination with paclitaxel |
paclitaxel | classic chemotherapy; | commonly used in HGSC alone or in combination with cisplatin |
taxane antimicrotubule agent | ||
panobinostat | epigenetic therapy; histone deacetylase inhibitor | improves efficacy of the cisplatin–paclitaxel combination in preclinical models [27] |
suberoylanilide hydroxamic acid/vorinostat | epigenetic therapy; histone deacetylase inhibitor | improves efficacy of paclitaxel combination in preclinical models [28] |
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Bilbao, M.; Katz, C.; Kass, S.L.; Smith, D.; Hunter, K.; Warshal, D.; Aikins, J.K.; Ostrovsky, O. Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time. Biomolecules 2021, 11, 1711. https://doi.org/10.3390/biom11111711
Bilbao M, Katz C, Kass SL, Smith D, Hunter K, Warshal D, Aikins JK, Ostrovsky O. Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time. Biomolecules. 2021; 11(11):1711. https://doi.org/10.3390/biom11111711
Chicago/Turabian StyleBilbao, Michelle, Chelsea Katz, Stephanie L. Kass, Devon Smith, Krystal Hunter, David Warshal, James K. Aikins, and Olga Ostrovsky. 2021. "Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time" Biomolecules 11, no. 11: 1711. https://doi.org/10.3390/biom11111711