Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.
Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.
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DOI：
10.1371/journal.pone.0141919
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Seo JH
中科院分区：
文献类型：
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作者：
An H;Kim JY;Oh E;Lee N;Cho Y;Seo JH
三阴性乳腺癌 (TNBC) 是一种侵袭性肿瘤亚型，具有丰富的 CD44+/CD24- 干细胞样群。盐霉素是一种抗生素，已被证明可以靶向癌症干细胞 (CSC)；然而，所涉及的作用机制尚未得到很好的描述。本研究的目的是研究盐霉素对 MDA-MB-231 乳腺癌细胞的细胞死亡、迁移和侵袭以及 CSC 样特性的影响。在不依赖锚定的生长过程中，盐霉素显着诱导失巢凋亡敏感性，并伴有 caspase-3 和 caspase-8 激活以及 PARP 裂解。盐霉素治疗还引起细胞迁移和侵袭的显着抑制，同时下调 MMP-9 和 MMP-2 mRNA 水平。值得注意的是，盐霉素抑制了球体的形成，并在不依赖锚定的生长过程中有效减少了 CD44+/CD24- 茎样群。这些观察结果与 STAT3 磷酸化 (Tyr705) 的抑制有关。此外，盐霉素攻击强烈抑制白介素 6 (IL-6) 诱导的 STAT3 激活。这些发现支持盐霉素可能通过抑制 STAT3 激活而有效靶向乳腺癌干细胞样细胞的观点。
Triple-negative breast cancer (TNBC) is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC); however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705). Furthermore, interleukin-6 (IL-6)-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.