Selenium inhibits growth of trastuzumab-resistant human breast cancer cells via downregulation of Akt and beclin-1
- 주제(기타) Multidisciplinary Sciences
- 설명문(일반) [Woo, Joohyun; Moon, Byung-In; Kwon, Hyungju; Lim, Woosung] Ewha Womans Univ, Dept Surg, Coll Med, Seoul, South Korea; [Kim, Jong Bin; Cho, Taeeun; Yoo, Eun Hye] Ewha Inst Convergence Med, Seoul, South Korea
- 등재 SCIE, SCOPUS
- OA유형 gold, Green Published
- 발행기관 PUBLIC LIBRARY SCIENCE
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183697
- 본문언어 영어
- Published As http://dx.doi.org/10.1371/journal.pone.0257298
- PubMed https://pubmed.ncbi.nlm.nih.gov/34525121
초록/요약
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.
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