Li Xiuli, Zhou Na, Wang Jin, Liu Zhijie, Wang Xiaohui, Zhang Qin, Liu Qingyan, Gao Lifeng, Wang Rong
Key Laboratory of Pharmacology, Chifeng University, Hongshan, Chifeng, Inner Mongolia 024000, China.
Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266061, China.
Life Sci. 2018 Mar 1;196:56-62. doi: 10.1016/j.lfs.2018.01.014. Epub 2018 Jan 21.
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.
We examined changes in the cluster of differentiation CD44/CD24CSC population and behavior using the breast cancer cell line MCF-7.
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 α 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.
These results indicated that CSCs are potential therapeutic targets for quercetin treatment of breast cancer.
癌症干细胞（CSCs）被认为是癌症复发、转移和进展的主要来源，也是开发新型抗癌药物和治疗策略的重要靶点。本研究旨在探讨抗癌类黄酮槲皮素对乳腺CSCs的治疗效果。
我们使用乳腺癌细胞系MCF-7检测了分化簇CD44/CD24 CSC群体及行为的变化。
我们的结果表明，CD44/CD24群体中的细胞活力、克隆形成、乳腺球生成及裸鼠肿瘤转移均受到抑制，并且槲皮素处理后MCF-7细胞出现G1期阻滞。此外，槲皮素处理后细胞周期蛋白D1和B细胞淋巴瘤-2表达受到抑制，而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）/蛋白激酶B（Akt）/雷帕霉素哺乳动物靶蛋白（mTOR）信号通路在CD44/CD24活力和克隆形成受到抑制的同时被下调。我们的研究结果表明，槲皮素处理通过抑制PI3K/Akt/mTOR信号通路，相对于正常癌细胞，促进了与CSCs相关的较弱恶性活性。
这些结果表明，CSCs是槲皮素治疗乳腺癌的潜在治疗靶点。
