Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-KB inhibition by suppressin IKKγ expression
Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-KB inhibition by suppressin IKKγ expression
复制标题
姜黄素通过抑制 IKKgamma 表达，通过抑制 NF-KappaB 增强喉鳞状细胞癌的放射敏感性
DOI：
10.1080/10799893.2020.1767649
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发表时间：
2020-06-02
影响因子：
2.8
通讯作者：
Luo, Zhi-guo
中科院分区：
文献类型：
--
作者：
Deng, Xin-zhou;Geng, Shan-shan;Luo, Zhi-guo
背景：姜黄素与放射治疗联合使用，可提高放射敏感性。目的：探讨IKK γ-NF-κ B信号通路在姜黄素增强喉鳞状细胞癌（LSCC）细胞放射敏感性中的作用。IKK γ siRNA和质粒用于改变IKK γ表达。CCK 8测定用于检测细胞活力。结果：姜黄素能显著增强照射诱导的喉癌细胞株Hep 2和Hep 2-max的DNA损伤和凋亡，同时减弱其克隆形成能力，并能诱导Hep 2和Hep 2-max细胞凋亡。与Hep 2细胞相比，Hep 2-max细胞对姜黄素的敏感性更高。姜黄素通过抑制IKK γ表达而不是IKKa和IKK γ抑制辐射诱导的NF-κ B活化。IKK γ的过表达降低了辐射诱导的DNA损伤和凋亡，同时促进了Hep 2和Hep 2-max细胞的克隆形成能力。IKK γ过表达进一步增加NF-κ B下游基因Bcl-XL、Bcl-2和细胞周期蛋白D1的表达。相反，IKK γ沉默增强辐射诱导的DNA损伤和凋亡，但促进Hep 2和Hep 2-max细胞的克隆形成。结论：姜黄素通过抑制IKK γ的表达，抑制NF-κ B B，增强喉鳞癌的放射敏感性。
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 IKK gamma-NF-kappa B 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. IKK gamma siRNA and plasmid were used to change IKK gamma 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 weak-ening 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-kappa B activation by suppressing IKK gamma expression, but not IKKa and IKK gamma. Overexpression of IKK gamma decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKK gamma overexpression further increased expression of NF-kappa B downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKK gamma silencing enhanced irradiation-induced DNA dam-age and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKK gamma silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1.Conclusions: Curcumin enhances LSCC radiosensitivity via NF-kappa B inhibition by suppressing IKK gamma expression.