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NF-κB 抑制通过 IκBα/AR 信号通路通过光热效应促进雄激素非依赖性前列腺癌细胞凋亡。

NF-κB inhibition promotes apoptosis in androgen-independent prostate cancer cells by the photothermal effect via the IκBα/AR signaling pathway.

机构信息

Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun 130033, China.

出版信息

Biomater Sci. 2019 May 28;7(6):2559-2570. doi: 10.1039/c8bm01007b.

DOI:10.1039/c8bm01007b
PMID:30977484
Abstract

The photothermal response of nanomaterials provides a basis for many biomedical applications, including diagnosis (e.g., biosensor and photoacoustic imaging) and treatment (e.g., drug delivery and photothermal therapy). The use of nano-materials for cancer phototherapy (solid tumor ablation) can cause cell necrosis and apoptosis. However, photothermal effects using the same material can differ among tumor cell types, and the molecular mechanisms underlying these differences are not clear. We used polydopamine (PDA)-coated branched Au-Ag nanoparticles (Au-Ag@PDA NPs) for the photothermal treatment of two prostate cancer cell lines. The therapeutic effect was evaluated by CCK8, flow cytometry, and expression analyses of related genes by western blotting. Photothermal therapy resulted in oxidative stress in prostate cancer cells and activated the mitochondrial-related apoptosis pathway, increasing the Bax expression. In addition, we observed a greater photothermal treatment effect on the androgen-dependent cells LNCaP than the androgen-independent cells DU145. Pretreatment with an inhibitor of the NF-κB signaling pathway (BAY 11-7082) enhanced the expression of BAX in the DU145 cells and increased the sensitivity of the cells to the heat treatment of Au-Ag@PDA NPs both in vitro and in vivo. Our findings explain the differences in the observed effects of photothermal therapy and provide the direction for further improvements to this strategy.

摘要

纳米材料的光热响应为许多生物医学应用提供了基础,包括诊断(例如生物传感器和光声成像)和治疗(例如药物输送和光热疗法)。纳米材料在癌症光疗(实体肿瘤消融)中的应用可以导致细胞坏死和凋亡。然而,使用相同材料的光热效应在不同的肿瘤细胞类型中有所不同,并且这些差异的分子机制尚不清楚。我们使用聚多巴胺(PDA)包覆的支化 Au-Ag 纳米颗粒(Au-Ag@PDA NPs)对两种前列腺癌细胞系进行光热治疗。通过 CCK8、流式细胞术以及 Western blot 分析相关基因的表达来评估治疗效果。光热治疗导致前列腺癌细胞发生氧化应激,并激活线粒体相关的凋亡途径,增加 Bax 表达。此外,我们观察到雄激素依赖性细胞 LNCaP 对光热治疗的效果优于雄激素非依赖性细胞 DU145。用 NF-κB 信号通路抑制剂(BAY 11-7082)预处理可增强 DU145 细胞中 Bax 的表达,并提高细胞对 Au-Ag@PDA NPs 热疗的敏感性,无论是在体外还是体内。我们的研究结果解释了光热治疗观察到的效果差异,并为进一步改进该策略提供了方向。

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