Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.

The response rate to treatment with trastuzumab (Tz), a recombinant humanized anti-HER2 monoclonal antibody, is only 12-34% despite demonstrated effectiveness on improving the survival of patients with HER2-positive breast cancers. Selenium has an antitumor effect against cancer cells and can play a...

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Autores principales:	Joohyun Woo, Jong Bin Kim, Taeeun Cho, Eun Hye Yoo, Byung-In Moon, Hyungju Kwon, Woosung Lim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/78b47d50ead644189f86b73bdae4f555
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spelling	oai:doaj.org-article:78b47d50ead644189f86b73bdae4f5552021-12-02T20:06:16ZSelenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.1932-620310.1371/journal.pone.0257298https://doaj.org/article/78b47d50ead644189f86b73bdae4f5552021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257298https://doaj.org/toc/1932-6203The response rate to treatment with trastuzumab (Tz), a recombinant humanized anti-HER2 monoclonal antibody, is only 12-34% despite demonstrated effectiveness on improving the survival of patients with HER2-positive breast cancers. Selenium has an antitumor effect against cancer cells and can play a cytoprotective role on normal cells. This study investigated the effect of selenium on HER2-positive breast cancer cells and the mechanism in relation to the response of the cells to Tz. HER2-positive breast cancer cell lines, SK-BR-3 as trastuzumab-sensitive cells, and JIMT-1 as Tz-resistant cells were treated with Tz and sodium selenite (selenite). Cell survival rates and expression of Her2, Akt, and autophagy-related proteins, including LC3B and beclin 1, in both cell lines 72 h after treatment were evaluated. Significant cell death was induced at different concentrations of selenite in both cell lines. A combined effect of selenite and Tz at 72 h was similar to or significantly greater than each drug alone. The expression of phosphorylated Akt (p-Akt) was decreased in JIMT-1 after combination treatment compared to that after only Tz treatment, while p-Akt expression was increased in SK-BR-3. The expression of beclin1 increased particularly in JIMT-1 after only Tz treatment and was downregulated by combination treatment. These results showed that combination of Tz and selenite had an antitumor effect in Tz-resistant breast cancer cells through downregulation of phosphorylated Akt and beclin1-related autophagy. Selenite might be a potent drug to treat Tz-resistant breast cancer by several mechanisms.Joohyun WooJong Bin KimTaeeun ChoEun Hye YooByung-In MoonHyungju KwonWoosung LimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257298 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joohyun Woo Jong Bin Kim Taeeun Cho Eun Hye Yoo Byung-In Moon Hyungju Kwon Woosung Lim Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.
description	The response rate to treatment with trastuzumab (Tz), a recombinant humanized anti-HER2 monoclonal antibody, is only 12-34% despite demonstrated effectiveness on improving the survival of patients with HER2-positive breast cancers. Selenium has an antitumor effect against cancer cells and can play a cytoprotective role on normal cells. This study investigated the effect of selenium on HER2-positive breast cancer cells and the mechanism in relation to the response of the cells to Tz. HER2-positive breast cancer cell lines, SK-BR-3 as trastuzumab-sensitive cells, and JIMT-1 as Tz-resistant cells were treated with Tz and sodium selenite (selenite). Cell survival rates and expression of Her2, Akt, and autophagy-related proteins, including LC3B and beclin 1, in both cell lines 72 h after treatment were evaluated. Significant cell death was induced at different concentrations of selenite in both cell lines. A combined effect of selenite and Tz at 72 h was similar to or significantly greater than each drug alone. The expression of phosphorylated Akt (p-Akt) was decreased in JIMT-1 after combination treatment compared to that after only Tz treatment, while p-Akt expression was increased in SK-BR-3. The expression of beclin1 increased particularly in JIMT-1 after only Tz treatment and was downregulated by combination treatment. These results showed that combination of Tz and selenite had an antitumor effect in Tz-resistant breast cancer cells through downregulation of phosphorylated Akt and beclin1-related autophagy. Selenite might be a potent drug to treat Tz-resistant breast cancer by several mechanisms.
format	article
author	Joohyun Woo Jong Bin Kim Taeeun Cho Eun Hye Yoo Byung-In Moon Hyungju Kwon Woosung Lim
author_facet	Joohyun Woo Jong Bin Kim Taeeun Cho Eun Hye Yoo Byung-In Moon Hyungju Kwon Woosung Lim
author_sort	Joohyun Woo
title	Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.
title_short	Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.
title_full	Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.
title_fullStr	Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.
title_full_unstemmed	Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.
title_sort	selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of akt and beclin-1.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/78b47d50ead644189f86b73bdae4f555
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Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1.

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