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Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1
- Title
- Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1
- Authors
- Woo, Joohyun; Kim, Jong Bin; Cho, Taeeun; Yoo, Eun Hye; Moon, Byung-In; Kwon, Hyungju; Lim, Woosung
- Ewha Authors
- 유은희; 문병인; 임우성; 권형주; 우주현
- SCOPUS Author ID
- 유은희; 문병인; 임우성; 권형주; 우주현
- Issue Date
- 2021
- Journal Title
- PLOS ONE
- ISSN
- 1932-6203
- Citation
- PLOS ONE vol. 16, no. 9
- Publisher
- PUBLIC LIBRARY SCIENCE
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.1371/journal.pone.0257298
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
- Files in This Item:
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journal.pone.0257298.pdf(2.32 MB)
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