Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.

<h4>Background and aim</h4>As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the...

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Autores principales:	Luping Gao, Yuji Morine, Shinichiro Yamada, Yu Saito, Tetsuya Ikemoto, Kazunori Tokuda, Chie Takasu, Katsuki Miyazaki, Mitsuo Shimada
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77a88510e3f24172b46a4826846c122e
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spelling	oai:doaj.org-article:77a88510e3f24172b46a4826846c122e2021-12-02T20:08:33ZNrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.1932-620310.1371/journal.pone.0256755https://doaj.org/article/77a88510e3f24172b46a4826846c122e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0256755https://doaj.org/toc/1932-6203<h4>Background and aim</h4>As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line.<h4>Methods</h4>A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again.<h4>Results</h4>Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced.<h4>Conclusion</h4>Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.Luping GaoYuji MorineShinichiro YamadaYu SaitoTetsuya IkemotoKazunori TokudaChie TakasuKatsuki MiyazakiMitsuo ShimadaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0256755 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luping Gao Yuji Morine Shinichiro Yamada Yu Saito Tetsuya Ikemoto Kazunori Tokuda Chie Takasu Katsuki Miyazaki Mitsuo Shimada Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
description	<h4>Background and aim</h4>As a multiple tyrosine kinase inhibitor, sorafenib is widely used to treat hepatocellular carcinoma (HCC), but patients frequently face resistance problems. Because the mechanism controlling sorafenib-resistance is not well understood, this study focused on the connection between tumor characteristics and the Nrf2 signaling pathway in a sorafenib-resistant HCC cell line.<h4>Methods</h4>A sorafenib-resistant HCC cell line (Huh7) was developed by increasing the dose of sorafenib in the culture medium until the target concentration was reached. Cell morphology, migration/invasion rates, and expression of stemness-related and ATP-binding cassette (ABC) transporter genes were compared between sorafenib-resistant Huh7 cells and parental Huh7 cells. Next, a small interfering RNA was used to knock down Nrf2 expression in sorafenib-resistant Huh7 cells, after which cell viability, stemness, migration, and ABC transporter gene expression were examined again.<h4>Results</h4>Proliferation, migration, and invasion rates of sorafenib-resistant Huh7 cells were significantly increased relative to the parental cells with or without sorafenib added to the medium. The expression levels of stemness markers and ABC transporter genes were up-regulated in sorafenib-resistant cells. After Nrf2 was knocked down in sorafenib-resistant cells, cell migration and invasion rates were reduced, and expression levels of stemness markers and ABC transporter genes were reduced.<h4>Conclusion</h4>Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant HCC cells.
format	article
author	Luping Gao Yuji Morine Shinichiro Yamada Yu Saito Tetsuya Ikemoto Kazunori Tokuda Chie Takasu Katsuki Miyazaki Mitsuo Shimada
author_facet	Luping Gao Yuji Morine Shinichiro Yamada Yu Saito Tetsuya Ikemoto Kazunori Tokuda Chie Takasu Katsuki Miyazaki Mitsuo Shimada
author_sort	Luping Gao
title	Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
title_short	Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
title_full	Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
title_fullStr	Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
title_full_unstemmed	Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
title_sort	nrf2 signaling promotes cancer stemness, migration, and expression of abc transporter genes in sorafenib-resistant hepatocellular carcinoma cells.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/77a88510e3f24172b46a4826846c122e
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Nrf2 signaling promotes cancer stemness, migration, and expression of ABC transporter genes in sorafenib-resistant hepatocellular carcinoma cells.

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