Quercetin suppresses breast cancer stem cells (CD44+/CD24-) by inhibiting the PI3K/Akt/mTOR-signaling pathway
Quercetin suppresses breast cancer stem cells (CD44+/CD24-) by inhibiting the PI3K/Akt/mTOR-signaling pathway
复制标题
槲皮素通过抑制 PI3K/Akt/mTOR 信号通路来抑制乳腺癌干细胞 (CD44 /CD24â)
DOI：
10.1016/j.lfs.2018.01.014
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发表时间：
2018-03-01
期刊：
影响因子：
6.1
通讯作者：
Wang, Rong
中科院分区：
文献类型：
--
作者：
Li, Xiuli;Zhou, Na;Wang, Rong
目的：癌症干细胞（CSC）被认为是癌症复发、转移和进展的主要来源，是开发新型抗癌药物和治疗策略的重要靶点。本研究的目的是探讨抗癌类黄酮槲皮素治疗乳腺CSC的效果。主要方法：我们使用乳腺癌细胞系MCF-7检测了分化簇CD44（+）/CD24（-）CSC群体和行为的变化。主要发现：我们的结果表明，在乳腺癌细胞中，细胞活力、克隆形成、乳腺球生成和裸鼠肿瘤转移均受到抑制。 CD44(+)/CD24(-)群体和MCF-7细胞在槲皮素处理后表现出G1期停滞。此外，槲皮素处理后，CyclinD1 和 B 细胞淋巴瘤-2 表达受到抑制，Bcl-2 样蛋白 4 表达增强。我们还观察到雌激素受体 α 和磷脂酰肌醇 3 激酶 (PI3K)/Akt/哺乳动物雷帕霉素靶蛋白 (mTOR) 信号传导下调，同时抑制 CD44(+)/CD24(-) 活力和克隆形成。我们的研究结果表明，与正常癌细胞中观察到的相比，槲皮素治疗通过抑制 PI3K/Akt/mTOR 信号通路，促进与 CSC 相关的较弱的恶性活性。意义：这些结果表明，CSC 是槲皮素治疗乳腺癌的潜在治疗靶点。
Aims: Cancer stem cells (CSCs) are considered the prime source of cancer recurrence, metastasis, and progression and represent important targets for developing novel anticancer agents and therapeutic strategies. The aim of this study was to investigate the effect of treating breast CSCs with the anticancer flavonoid, quercetin.Main methods: We examined changes in the cluster of differentiation CD44(+)/CD24(-)CSC population and behavior using the breast cancer cell line MCF-7.Key findings: Our results indicated that cell viability, clone formation, mammosphere generation, and nude mice tumor metastasis were inhibited in the CD44(+)/CD24(-)population and that MCF-7 cells exhibited G1-phase arrest after quercetin treatment. Additionally, CyclinD1 and B cell lymphoma-2 expression were suppressed and Bcl-2-like protein-4 expression was enhanced after quercetin treatment. We also observed that estrogen receptor alpha and phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling were downregulated concurrently with the inhibition of CD44(+)/CD24(-)viability and clone formation. Our findings suggested that quercetin treatment promoted weaker malignant activity associated with CSCs relative to that observed in normal cancer cells through its inhibition of the PI3K/Akt/mTOR-signaling pathway.Significance: These results indicated that CSCs are potential therapeutic targets for quercetin treatment of breast cancer.