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...

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Autores principales:	Michelle Bilbao, Chelsea Katz, Stephanie L. Kass, Devon Smith, Krystal Hunter, David Warshal, James K. Aikins, Olga Ostrovsky
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	high-grade serous ovarian cancer recurrent ovarian cancer chemoresistance platinum resistance taxane resistance spheroids Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c185411d397447509a2c8b6b0faa58f5
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spelling	oai:doaj.org-article:c185411d397447509a2c8b6b0faa58f52021-11-25T16:54:11ZEpigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time10.3390/biom111117112218-273Xhttps://doaj.org/article/c185411d397447509a2c8b6b0faa58f52021-11-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1711https://doaj.org/toc/2218-273XRecurrent 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.Michelle BilbaoChelsea KatzStephanie L. KassDevon SmithKrystal HunterDavid WarshalJames K. AikinsOlga OstrovskyMDPI AGarticlehigh-grade serous ovarian cancerrecurrent ovarian cancerchemoresistanceplatinum resistancetaxane resistancespheroidsMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1711, p 1711 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	high-grade serous ovarian cancer recurrent ovarian cancer chemoresistance platinum resistance taxane resistance spheroids Microbiology QR1-502
spellingShingle	high-grade serous ovarian cancer recurrent ovarian cancer chemoresistance platinum resistance taxane resistance spheroids Microbiology QR1-502 Michelle Bilbao Chelsea Katz Stephanie L. Kass Devon Smith Krystal Hunter David Warshal James K. Aikins Olga Ostrovsky Epigenetic Therapy Augments Classic Chemotherapy in Suppressing the Growth of 3D High-Grade Serous Ovarian Cancer Spheroids over an Extended Period of Time
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	article
author	Michelle Bilbao Chelsea Katz Stephanie L. Kass Devon Smith Krystal Hunter David Warshal James K. Aikins Olga Ostrovsky
author_facet	Michelle Bilbao Chelsea Katz Stephanie L. Kass Devon Smith Krystal Hunter David Warshal James K. Aikins Olga Ostrovsky
author_sort	Michelle Bilbao
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_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_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_sort	epigenetic therapy augments classic chemotherapy in suppressing the growth of 3d high-grade serous ovarian cancer spheroids over an extended period of time
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c185411d397447509a2c8b6b0faa58f5
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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

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