Abstract Context: Curcumin has shown efficacy in promoting radiosensitivity combined with radiotherapy. However, the role and mechanism of curcumin on radiosensitivity in laryngeal squamous cell cancer (LSCC) is largely unknown. Objective: The aim of our study is to explore the role of IKKγ-NF-κB signaling in curcumin enhancing LSCC cell radiosensitivity in vitro. Materials and methods: Curcumin and X-ray were used to induce cell DNA damage and apoptosis, or inhibit cell clone formation. IKKγ siRNA and plasmid were used to change IKKγ expression. The CCK8 assay was used to detect cell viability. Clone formation ability was analyzed using a clonogenic assay, cell apoptosis was examined using flow cytometry, an immunofluorescence assay was used to detect DNA damage, while mRNA and protein levels were assayed using real time PCR and western blotting, respectively. Results: Curcumin significantly enhanced irradiation-induced DNA damage and apoptosis, while weakening clone-forming abilities of LSCC cell line Hep2 and Hep2-max. Compared to Hep2 cells, Hep2-max cells are more sensitive to curcumin post-irradiation. Curcumin suppressed irradiation-induced NF-κB activation by suppressing IKKγ expression, but not IKKα and IKKβ. Overexpression of IKKγ decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKγ overexpression further increased expression of NF-κB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKγ silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKγ silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1. Conclusions: Curcumin enhances LSCC radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression.

中文翻译：

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姜黄素通过抑制 IKKγ 表达通过 NF-ΚB 抑制增强喉鳞状癌放射敏感性

摘要 背景：姜黄素联合放疗具有促进放射敏感性的疗效。然而，姜黄素对喉鳞状细胞癌 (LSCC) 放射敏感性的作用和机制在很大程度上是未知的。目的：我们研究的目的是探讨 IKKγ-NF-κB 信号在姜黄素体外增强 LSCC 细胞放射敏感性中的作用。材料与方法：姜黄素和X射线用于诱导细胞DNA损伤和凋亡，或抑制细胞克隆形成。IKKγ siRNA 和质粒用于改变 IKKγ 表达。CCK8测定用于检测细胞活力。使用克隆形成试验分析克隆形成能力，使用流式细胞术检查细胞凋亡，使用免疫荧光试验检测 DNA 损伤，同时使用实时 PCR 和蛋白质印迹分析 mRNA 和蛋白质水平，分别。结果：姜黄素显着增强辐射诱导的 DNA 损伤和细胞凋亡，同时削弱 LSCC 细胞系 Hep2 和 Hep2-max 的克隆形成能力。与 Hep2 细胞相比，Hep2-max 细胞对辐照后的姜黄素更敏感。姜黄素通过抑制 IKKγ 表达来抑制辐射诱导的 NF-κB 活化，但不抑制 IKKα 和 IKKβ。IKKγ 的过表达减少了辐射诱导的 DNA 损伤和细胞凋亡，同时促进了 Hep2 和 Hep2-max 细胞的克隆形成能力。IKKγ 过表达进一步增加了 NF-κB 下游基因 Bcl-XL、Bcl-2 和细胞周期蛋白 D1 的表达。相反，IKKγ 沉默增强了辐射诱导的 DNA 损伤和细胞凋亡，但促进了 Hep2 和 Hep2-max 细胞中的克隆形成。此外，IKKγ 沉默抑制了 Bcl-XL、Bcl-2 和细胞周期蛋白 D1 的表达。