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金纳米颗粒通过 MCF-7 乳腺癌细胞系中 Noxa 和 Bim 基因表达的差异来实现放射增敏和光疗作用。

Radiosensitizing and Phototherapeutic Effects of AuNPs are Mediated by Differential Noxa and Bim Gene Expression in MCF-7 Breast Cancer Cell Line.

出版信息

IEEE Trans Nanobioscience. 2021 Jan;20(1):20-27. doi: 10.1109/TNB.2020.3028562. Epub 2020 Dec 30.

Abstract

To compare the apoptotic efficiency of AuNPs, ionizing and non-ionizing radiotherapy, phototherapy, and AuNPs-ionizing-radiotherapy), MCF-7 cells were used as a model for luminal B subtypes of breast carcinoma. A mixture of AuNPs [66% of Au-nanospheres (AuNSs) and 34% of Au-nanorods (AuNRs)] was synthesized and characterized by optical spectroscopy, zeta potential, and transmission electron microscopy (TEM). MCF-7 were divided into six groups (triplicates); after each treatment, cell viability was tested by MTT assay and relative gene expression levels of Bim and Noxa proapoptotic markers were assayed by qRT-PCR. A dose-dependent significant reduction in cell viability of MCF-7 was detected by all examined treatment protocols. Lower viability detected at extended exposure (48 hours) to AuNPs ( [Formula: see text]/ml) was mediated by the upregulation of Noxa gene expression. AuNS and AuNR in vitro PTTs were mediated by differential expression of Bim and Noxa while AuNPs mixture had a combined effect on both Bim and Noxa. Cellular recovery was observed two days-post x-rays irradiation at does < 3 Gy. AuNPs showed dose enhancement factor (DEF) > 12 indicating a high radiosensitizing effect that was partially mediated by Noxa. In conclusion, AuNPs combined therapies exert better anti-proliferative effects via differential regulation of Noxa and Bim gene expressions.

摘要

为了比较 AuNPs、电离和非电离放射治疗、光疗以及 AuNPs-电离放射治疗的凋亡效率,将 MCF-7 细胞用作乳腺腔 B 型亚型的模型。合成了 AuNPs 的混合物(Au-纳米球 [AuNSs] 的 66%和 Au-纳米棒 [AuNRs] 的 34%),并通过光学光谱、Zeta 电位和透射电子显微镜(TEM)进行了表征。将 MCF-7 细胞分为六组(重复三次);在每种处理后,通过 MTT 测定法测试细胞活力,并通过 qRT-PCR 测定促凋亡标记物 Bim 和 Noxa 的相对基因表达水平。通过所有检查的处理方案都检测到 MCF-7 细胞活力的剂量依赖性显著降低。在延长暴露(48 小时)至 AuNPs([公式:见文本]/ml)时检测到更低的活力,这是由 Noxa 基因表达上调介导的。AuNS 和 AuNR 的体外 PTT 是由 Bim 和 Noxa 的差异表达介导的,而 AuNPs 混合物对两者均有综合作用。在 X 射线照射剂量<3 Gy 后两天观察到细胞恢复。AuNPs 显示出剂量增强因子(DEF)>12,表明具有高放射增敏作用,部分是由 Noxa 介导的。总之,AuNPs 联合治疗通过差异调节 Noxa 和 Bim 基因表达发挥更好的抗增殖作用。

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