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Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time
Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients’ lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortu...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615646/ https://www.ncbi.nlm.nih.gov/pubmed/34827710 http://dx.doi.org/10.3390/biom11111711 |
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author | Bilbao, Michelle Katz, Chelsea Kass, Stephanie L. Smith, Devon Hunter, Krystal Warshal, David Aikins, James K. Ostrovsky, Olga |
author_facet | Bilbao, Michelle Katz, Chelsea Kass, Stephanie L. Smith, Devon Hunter, Krystal Warshal, David Aikins, James K. Ostrovsky, Olga |
author_sort | Bilbao, Michelle |
collection | PubMed |
description | Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients’ lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture. |
format | Online Article Text |
id | pubmed-8615646 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86156462021-11-26 Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time Bilbao, Michelle Katz, Chelsea Kass, Stephanie L. Smith, Devon Hunter, Krystal Warshal, David Aikins, James K. Ostrovsky, Olga Biomolecules Article Recurrent high-grade serous ovarian cancer (HGSC) is clinically very challenging and prematurely shortens patients’ lives. Recurrent ovarian cancer is characterized by high tumor heterogeneity; therefore, it is susceptible to epigenetic therapy in classic 2D tissue culture and rodent models. Unfortunately, this success has not translated well into clinical trials. Utilizing a 3D spheroid model over a period of weeks, we were able to compare the efficacy of classic chemotherapy and epigenetic therapy on recurrent ovarian cancer cells. Unexpectedly, in our model, a single dose of paclitaxel alone caused the exponential growth of recurrent high-grade serous epithelial ovarian cancer over a period of weeks. In contrast, this effect is not only opposite under treatment with panobinostat, but panobinostat reverses the repopulation of cancer cells following paclitaxel treatment. In our model, we also demonstrate differences in the drug-treatment sensitivity of classic chemotherapy and epigenetic therapy. Moreover, 3D-derived ovarian cancer cells demonstrate induced proliferation, migration, invasion, cancer colony formation and chemoresistance properties after just a single exposure to classic chemotherapy. To the best of our knowledge, this is the first evidence demonstrating a critical contrast between short and prolonged post-treatment outcomes following classic chemotherapy and epigenetic therapy in recurrent high-grade serous ovarian cancer in 3D culture. MDPI 2021-11-17 /pmc/articles/PMC8615646/ /pubmed/34827710 http://dx.doi.org/10.3390/biom11111711 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bilbao, Michelle Katz, Chelsea Kass, Stephanie L. Smith, Devon Hunter, Krystal Warshal, David Aikins, James K. Ostrovsky, Olga Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time |
title | Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time |
title_full | Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time |
title_fullStr | Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time |
title_full_unstemmed | Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time |
title_short | Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time |
title_sort | epigenetic therapy augments classic chemotherapy in suppressing the growth of 3d high-grade serous ovarian cancer spheroids over an extended period of time |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615646/ https://www.ncbi.nlm.nih.gov/pubmed/34827710 http://dx.doi.org/10.3390/biom11111711 |
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