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Anticancer properties of novel zinc oxide quantum dot nanoparticles against breast cancer stem-like cells.
Anti-Cancer Drugs ( IF 2.3 ) Pub Date : 2021-08-19 , DOI: 10.1097/cad.0000000000001207
Zahra Fakhroueian 1 , Sadegh Rajabi 2 , Niloufar Salehi 3 , Mostafa Rezaei Tavirani 4 , Shokoofe Noori 3 , Mitra Nourbakhsh 5, 6
Affiliation  

Cancer stem cells (CSCs) play an essential role in cancer development, metastasis, relapse, and resistance to treatment. In this article, the effects of three synthesized ZnO nanofluids on proliferation, apoptosis, and stemness markers of breast cancer stem-like cells are reported. The antiproliferative and apoptotic properties of ZnO nanoparticles were evaluated on breast cancer stem-like cell-enriched mammospheres by MTS assay and flowcytometry, respectively. The expression of stemness markers, including WNT1, NOTCH1, β-catenin, CXCR4, SOX2, and ALDH3A1 was assessed by real-time PCR. Western blotting was used to analyze the phosphorylation of Janus kinase 2 (JAK2) and Signal Transducer and Activator of Transcription 3 (STAT3). Markers of stemness were significantly decreased by ZnO nanofluids, especially sample (c) with code ZnO-148 with a different order of addition of polyethylene glycol solution at the end of formulation, which considerably decreased all the markers compared to the controls. All the studied ZnO nanofluids considerably reduced viability and induced apoptosis of spheroidal and parental cells, with ZnO-148 presenting the most effective activity. Using CD95L as a death ligand and ZB4 as an extrinsic apoptotic pathway blocker, it was revealed that none of the nanoparticles induced apoptosis through the extrinsic pathway. Results also showed a marked inhibition of the JAK/STAT pathway by ZnO nanoparticles; confirmed by downregulation of Mcl-1 and Bcl-XL expression. The present data demonstrated that ZnO nanofluids could combat breast CSCs via decreasing stemness markers, stimulating apoptosis, and suppressing JAK/STAT activity.

中文翻译:

新型氧化锌量子点纳米粒子对乳腺癌干细胞的抗癌特性。

癌症干细胞(CSC)在癌症的发展、转移、复发和治疗耐药中发挥着重要作用。在本文中,报道了三种合成的 ZnO 纳米流体对乳腺癌干样细胞的增殖、凋亡和干性标志物的影响。分别通过 MTS 测定和流式细胞术评估了 ZnO 纳米粒子在富含乳腺癌干细胞的乳腺球上的抗增殖和凋亡特性。通过实时 PCR 评估干性标记的表达,包括 WNT1、NOTCH1、β-连环蛋白、CXCR4、SOX2 和 ALDH3A1。使用蛋白质印迹分析 Janus 激酶 2 (JAK2) 和信号转导和转录激活因子 3 (STAT3) 的磷酸化。ZnO 纳米流体显着降低了干性标记,特别是代码为 ZnO-148 的样品 (c),在配制结束时以不同顺序添加聚乙二醇溶液,与对照相比,这显着降低了所有标记。所有研究的 ZnO 纳米流体都会显着降低球状细胞和亲代细胞的活力并诱导细胞凋亡,其中 ZnO-148 表现出最有效的活性。使用CD95L作为死亡配体和ZB4作为外源性细胞凋亡途径阻断剂,结果表明,没有任何纳米颗粒通过外源性途径诱导细胞凋亡。结果还表明,ZnO 纳米粒子对 JAK/STAT 通路有显着抑制作用;通过 Mcl-1 和 Bcl-XL 表达的下调证实。目前的数据表明,ZnO 纳米流体可以通过减少干细胞标记、刺激细胞凋亡和抑制 JAK/STAT 活性来对抗乳腺 CSC。
更新日期:2021-08-19
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