异长春花碱抑制乳腺癌干细胞样特性和 STAT3 信号通路。
Isoharringtonine inhibits breast cancer stem-like properties and STAT3 signaling.
机构信息
Institute of Physical Science and Information Technology, Anhui University, 230601, China; Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, China.
出版信息
Biomed Pharmacother. 2018 Jul;103:435-442. doi: 10.1016/j.biopha.2018.04.076. Epub 2018 Apr 24.
OBJECTIVES
Breast cancer stem cells (BCSCs) contribute to breast cancer progression, relapse, and treatment resistance. Identification of the natural inhibitory components of BCSCs is therefore critical for clinical treatment. Here, we investigated whether isoharringtonine (IHT) had inhibitory effects on BCSCs in breast cancer cell lines.
METHODS
HCC1806, HCC1937, and MCF7 cells were treated with IHT. The proliferation and the migration of cells were detected by MTS assay and wound healing migration assay, respectively. The proportions of BCSCs were determined by flow cytometry and tumor sphere formation assay. Using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, the expression of Nanog and activation of STAT3 were detected, respectively.
RESULTS
Results showed that IHT inhibited the proliferation of HCC1806, HCC1937, and MCF-7 cells, and suppressed the migration of HCC1806 and HCC1937 cells in a dose-dependent manner. IHT treatment decreased the proportion of BCSCs in MCF-7, HCC1806, and HCC1937 cells. In addition, the mRNA level of Nanong was significantly downregulated after IHT treatment. We also found an inhibitory effect of IHT on STAT3 activation.
CONCLUSION
IHT inhibited the proliferation, migration, and BCSC proportion of breast cancer cell lines via inhibition of the STAT3/Nanong pathway.
目的
乳腺癌干细胞（BCSCs）促进乳腺癌的进展、复发和治疗抵抗。因此，鉴定 BCSCs 的天然抑制成分对于临床治疗至关重要。在这里，我们研究了异长春花碱（IHT）是否对乳腺癌细胞系中的 BCSCs 具有抑制作用。
方法
用 IHT 处理 HCC1806、HCC1937 和 MCF7 细胞。通过 MTS 测定和划痕愈合迁移测定分别检测细胞的增殖和迁移。通过流式细胞术和肿瘤球体形成测定确定 BCSCs 的比例。通过实时定量聚合酶链反应（qRT-PCR）和 Western blot 分别检测 Nanog 的表达和 STAT3 的激活。
结果
结果表明，IHT 抑制 HCC1806、HCC1937 和 MCF-7 细胞的增殖，并呈剂量依赖性抑制 HCC1806 和 HCC1937 细胞的迁移。IHT 处理降低了 MCF-7、HCC1806 和 HCC1937 细胞中 BCSCs 的比例。此外，IHT 处理后 Nanong 的 mRNA 水平显著下调。我们还发现 IHT 对 STAT3 激活有抑制作用。
结论
IHT 通过抑制 STAT3/Nanog 通路抑制乳腺癌细胞系的增殖、迁移和 BCSC 比例。
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