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富含染料木黄酮的异黄酮苷元通过抑制 NF-κB 信号通路抑制肺癌生长。

Daidzein-rich isoflavones aglycone inhibits lung cancer growth through inhibition of NF-κB signaling pathway.

机构信息

Department of Cardiothoracic Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, China.

Department of Respiratory Medicine, First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, China.

出版信息

Immunol Lett. 2020 Jun;222:67-72. doi: 10.1016/j.imlet.2020.03.004. Epub 2020 Mar 18.

Abstract

To develop anti-tumor agents for lung cancer, we aim to characterize a herbal compound, daidzein-rich isoflavones aglycone (DRIA), in inhibiting the proliferation and NF-κB signaling pathway of lung cancer. MTT and colony formation assays were used to analyze the proliferation of lung cancer cells in presence of DRIA treatment, which showed that DRIA dose-dependently inhibited the proliferation and colony formation of lung cancer cells. Enzyme-linked immunosorbent assay revealed that interleukin-6 (IL6) and interleukin-8 (IL-8) levels were reduced by DRIA. p65-NFκB expression and activation, which was enhanced by TNF-α and C/EBPβ treatment, were attenuated by DRIA. Exogenous tumor necrosis factor-α (TNF-α) and CCAAT/enhancer binding protein (C/EBPβ) were used to enhance NF-κB signaling in cells, and the effects of DRIA in attenuating NF-κB signaling were assessed by analyzing p65-NFκB expression in mRNA and protein levels, using quantitative real-time PCR (qRT-PCR), western blot and immunofluorescence staining. immunohistochemical staining revealed that Ki-67 and p65-NF-κB levels in A594 tumor xenografts of A594 tumors were also reduced by DRIA treatment in mice. Our data indicates that DRIA is effective in inhibiting the proliferation and NFκB signaling of lung cancer both in vitro and in vivo.

摘要

为了开发治疗肺癌的抗肿瘤药物,我们旨在研究一种草药化合物,大豆苷元丰富的异黄酮苷元(DRIA),以抑制肺癌细胞的增殖和 NF-κB 信号通路。MTT 和集落形成实验用于分析 DRIA 处理后肺癌细胞的增殖情况,结果表明 DRIA 呈剂量依赖性地抑制肺癌细胞的增殖和集落形成。酶联免疫吸附试验显示 DRIA 降低了白细胞介素-6(IL6)和白细胞介素-8(IL-8)的水平。TNF-α 和 C/EBPβ 处理增强的 p65-NFκB 表达和激活被 DRIA 减弱。外源性肿瘤坏死因子-α(TNF-α)和 CCAAT/增强子结合蛋白(C/EBPβ)被用于增强细胞中的 NF-κB 信号,通过分析 p65-NFκB 在 mRNA 和蛋白水平上的表达,使用定量实时 PCR(qRT-PCR)、western blot 和免疫荧光染色来评估 DRIA 在减弱 NF-κB 信号中的作用。免疫组化染色显示,DRIA 处理还降低了小鼠 A594 肿瘤异种移植中 A594 肿瘤的 Ki-67 和 p65-NF-κB 水平。我们的数据表明,DRIA 可有效抑制肺癌的增殖和 NFκB 信号通路,无论是在体外还是体内。

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