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5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy

Colorectal cancer (CRC) is a major cause of mortality that can be treated effectively with chemotherapy and radiotherapy, although resistance to these therapeutic modalities often occurs. Tumor-treating fields (TTFields) can block tumor growth by selectively impairing tumor cell division. In this st...

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Autores principales: Lee, Yeon-Joo, Cho, Jae-Min, Sai, Sei, Oh, Ju Yeon, Park, Ji-Ae, Oh, Se Jong, Park, Misun, Kwon, Junhye, Shin, Ui Sup, Baek, Jeong-Hwa, Lim, Sun Ha, Song, Jie-Young, Hwang, Sang-Gu, Kim, Eun Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966590/
https://www.ncbi.nlm.nih.gov/pubmed/31842288
http://dx.doi.org/10.3390/cancers11121999
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author Lee, Yeon-Joo
Cho, Jae-Min
Sai, Sei
Oh, Ju Yeon
Park, Ji-Ae
Oh, Se Jong
Park, Misun
Kwon, Junhye
Shin, Ui Sup
Baek, Jeong-Hwa
Lim, Sun Ha
Song, Jie-Young
Hwang, Sang-Gu
Kim, Eun Ho
author_facet Lee, Yeon-Joo
Cho, Jae-Min
Sai, Sei
Oh, Ju Yeon
Park, Ji-Ae
Oh, Se Jong
Park, Misun
Kwon, Junhye
Shin, Ui Sup
Baek, Jeong-Hwa
Lim, Sun Ha
Song, Jie-Young
Hwang, Sang-Gu
Kim, Eun Ho
author_sort Lee, Yeon-Joo
collection PubMed
description Colorectal cancer (CRC) is a major cause of mortality that can be treated effectively with chemotherapy and radiotherapy, although resistance to these therapeutic modalities often occurs. Tumor-treating fields (TTFields) can block tumor growth by selectively impairing tumor cell division. In this study, we investigated the mechanism by which 5-fluorouracil (5-FU) sensitizes tumor cells to TTFields. Human HCT116 and SW480 CRC cells were treated with 5-FU and/or TTFields, and characterized in vitro in terms of cell viability, apoptosis through reactive oxygen species production, autophagy, and metastatic potentials. The biological effects of 5-FU and/or TTFields were studied via positron emission tomography and computed tomography on xenograft tumor growth and were confirmed with organoid models of patients. Our results revealed that combination treatment with 5-FU and TTFields increased the efficiency of TTFields therapy in colon cancer cells by downregulating signaling pathways associated with cell proliferation, survival, cell invasion, and migration while upregulating pathways mediating apoptosis and autophagic cell death. The novel mechanistic insights gleaned in this study suggest that combination therapy with TTFields and 5-FU may be effective in treating CRC, although safety and efficacy testing in patients with CRC will need to be performed before this strategy can be implemented clinically for TTF-sensitization.
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spelling pubmed-69665902020-02-04 5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy Lee, Yeon-Joo Cho, Jae-Min Sai, Sei Oh, Ju Yeon Park, Ji-Ae Oh, Se Jong Park, Misun Kwon, Junhye Shin, Ui Sup Baek, Jeong-Hwa Lim, Sun Ha Song, Jie-Young Hwang, Sang-Gu Kim, Eun Ho Cancers (Basel) Article Colorectal cancer (CRC) is a major cause of mortality that can be treated effectively with chemotherapy and radiotherapy, although resistance to these therapeutic modalities often occurs. Tumor-treating fields (TTFields) can block tumor growth by selectively impairing tumor cell division. In this study, we investigated the mechanism by which 5-fluorouracil (5-FU) sensitizes tumor cells to TTFields. Human HCT116 and SW480 CRC cells were treated with 5-FU and/or TTFields, and characterized in vitro in terms of cell viability, apoptosis through reactive oxygen species production, autophagy, and metastatic potentials. The biological effects of 5-FU and/or TTFields were studied via positron emission tomography and computed tomography on xenograft tumor growth and were confirmed with organoid models of patients. Our results revealed that combination treatment with 5-FU and TTFields increased the efficiency of TTFields therapy in colon cancer cells by downregulating signaling pathways associated with cell proliferation, survival, cell invasion, and migration while upregulating pathways mediating apoptosis and autophagic cell death. The novel mechanistic insights gleaned in this study suggest that combination therapy with TTFields and 5-FU may be effective in treating CRC, although safety and efficacy testing in patients with CRC will need to be performed before this strategy can be implemented clinically for TTF-sensitization. MDPI 2019-12-12 /pmc/articles/PMC6966590/ /pubmed/31842288 http://dx.doi.org/10.3390/cancers11121999 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lee, Yeon-Joo
Cho, Jae-Min
Sai, Sei
Oh, Ju Yeon
Park, Ji-Ae
Oh, Se Jong
Park, Misun
Kwon, Junhye
Shin, Ui Sup
Baek, Jeong-Hwa
Lim, Sun Ha
Song, Jie-Young
Hwang, Sang-Gu
Kim, Eun Ho
5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy
title 5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy
title_full 5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy
title_fullStr 5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy
title_full_unstemmed 5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy
title_short 5-Fluorouracil as a Tumor-Treating Field-Sensitizer in Colon Cancer Therapy
title_sort 5-fluorouracil as a tumor-treating field-sensitizer in colon cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6966590/
https://www.ncbi.nlm.nih.gov/pubmed/31842288
http://dx.doi.org/10.3390/cancers11121999
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