Oxymatrine diminishes the side population and inhibits the expression of β-catenin in MCF-7 breast cancer cells

Oxymatrine diminishes the side population and inhibits the expression of β-catenin in MCF-7 breast cancer cells
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DOI:
10.1007/s12032-010-9721-y
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发表时间:
2011-12-01
期刊:
影响因子:
3.4
通讯作者:
Lin, Hongsheng
Lin, Hongsheng
中科院分区:
医学4区
文献类型:
--
作者:
Zhang, Ying;Piao, Bingkui;Lin, Hongsheng

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癌症干细胞(CSCs)在癌症的发生和复发中起着至关重要的作用,因为它们对大多数细胞毒性药物具有抗性,并且能够无限增殖。植物生物碱氧化苦参碱具有许多生物活性,包括诱导细胞周期阻滞和细胞凋亡的能力,这使其成为靶向癌细胞的潜在有用药物。为了确定氧化苦参碱是否具有根除CSCs的有益药理特性,我们分析了氧化苦参碱对MCF-7乳腺癌细胞的影响。进行肿瘤干细胞样细胞(侧群,SP)鉴定和分选。观察氧化苦参碱对SP细胞和非SP细胞的抑制作用。结果表明,氧化苦参碱对MCF-7细胞的增殖有剂量依赖性,对SP细胞的增殖有抑制作用。通过分析胞质中总β -catenin和磷酸化β -catenin的表达,检测Wnt/ β -catenin信号通路,结果表明氧化苦参碱处理对MCF-7细胞的生长抑制作用可能是由于抑制了SP和Wnt/ β -catenin信号通路。氧化苦参碱是否可能成为一种有效的靶向乳腺CSCs的新型治疗药物有待进一步研究。
Cancer stem cells (CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most cytotoxic agents and able to proliferate indefinitely. The plant alkaloid oxymatrine has many biological activities including the ability to induce cell cycle arrest and apoptosis, which makes it a potentially useful agent for targeting cancer cells. In order to determine whether it has beneficial pharmacological properties to eradicate CSCs, we analyzed the effects of oxymatrine on MCF-7 breast cancer cells. Cancer stem-like cells' (side population, SP) identification and sorting were performed. The inhibitory effect of oxymatrine was evaluated on the sorted SP and non-SP cells. The results indicated that oxymatrine caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells. Wnt/beta-catenin signaling pathway was also examined by analyzing the expression of total beta-catenin and phosphorylated beta-catenin in cytoplasm, and the results showed that the growth inhibitory effects of oxymatrine treatment on MCF-7 cells may be due to the inhibition of SP and Wnt/beta-catenin signaling pathway. Further work is warranted to explore whether oxymatrine may be a useful novel therapeutic drug for targeting breast CSCs.