PMID- 32515250 OWN - NLM STAT- MEDLINE DCOM- 20210713 LR - 20210713 IS - 1532-4281 (Electronic) IS - 1079-9893 (Linking) VI - 40 IP - 6 DP - 2020 Dec TI - Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-KappaB inhibition by suppressing IKKgamma expression. PG - 541-549 LID - 10.1080/10799893.2020.1767649 [doi] AB - 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 IKKgamma-NF-kappaB 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. IKKgamma siRNA and plasmid were used to change IKKgamma 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-kappaB activation by suppressing IKKgamma expression, but not IKKalpha and IKKbeta. Overexpression of IKKgamma decreased irradiation-induced DNA damage and apoptosis, while promoting clone-forming abilities of Hep2 and Hep2-max cells. IKKgamma overexpression further increased expression of NF-kappaB downstream genes, Bcl-XL, Bcl-2, and cyclin D1. Conversely, IKKgamma silencing enhanced irradiation-induced DNA damage and apoptosis, but promoted clone formation in Hep2 and Hep2-max cells. Additionally, IKKgamma silencing inhibited expression of Bcl-XL, Bcl-2, and cyclin D1.Conclusions: Curcumin enhances LSCC radiosensitivity via NF-KappaB inhibition by suppressing IKKgamma expression. FAU - Deng, Xin-Zhou AU - Deng XZ AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. AD - HubeiKey Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Geng, Shan-Shan AU - Geng SS AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. AD - Postgraduate Training Base, Shiyan Taihe Hospital, Jinzhou Medical University, Shiyan, Hubei, PR China. FAU - Luo, Ming AU - Luo M AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Chai, Jing-Jing AU - Chai JJ AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Xu, Ying AU - Xu Y AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Chen, Chun-Li AU - Chen CL AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Qiu, Li AU - Qiu L AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Ke, Qing AU - Ke Q AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Duan, Qi-Wen AU - Duan QW AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Song, Shi-Mao AU - Song SM AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Shen, Li AU - Shen L AD - Department of Biochemistry, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan, Hubei, PR China. FAU - Luo, Zhi-Guo AU - Luo ZG AD - Department of Clinical Oncology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, PR China. LA - eng PT - Journal Article DEP - 20200609 PL - England TA - J Recept Signal Transduct Res JT - Journal of receptor and signal transduction research JID - 9509432 RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (IKBKG protein, human) RN - 0 (NF-kappa B) RN - 0 (Radiation-Sensitizing Agents) RN - EC 2.7.11.10 (I-kappa B Kinase) RN - IT942ZTH98 (Curcumin) SB - IM MH - Antineoplastic Agents/pharmacology MH - Apoptosis MH - Biomarkers, Tumor/genetics/metabolism MH - Carcinoma, Squamous Cell/drug therapy/metabolism/pathology/*radiotherapy MH - Cell Proliferation MH - Curcumin/*pharmacology MH - Gene Expression Regulation, Neoplastic MH - Humans MH - I-kappa B Kinase/*antagonists & inhibitors MH - Laryngeal Neoplasms/drug therapy/metabolism/pathology/*radiotherapy MH - NF-kappa B/*antagonists & inhibitors MH - Phosphorylation MH - Radiation Tolerance/*drug effects MH - Radiation-Sensitizing Agents/*pharmacology MH - Signal Transduction MH - Tumor Cells, Cultured OTO - NOTNLM OT - Curcumin OT - IKKgamma OT - NF-kappaB OT - laryngeal squamous carcinoma OT - radiosensitivity EDAT- 2020/06/10 06:00 MHDA- 2021/07/14 06:00 CRDT- 2020/06/10 06:00 PHST- 2020/06/10 06:00 [pubmed] PHST- 2021/07/14 06:00 [medline] PHST- 2020/06/10 06:00 [entrez] AID - 10.1080/10799893.2020.1767649 [doi] PST - ppublish SO - J Recept Signal Transduct Res. 2020 Dec;40(6):541-549. doi: 10.1080/10799893.2020.1767649. Epub 2020 Jun 9.