Curcumin potentiates laryngeal squamous carcinoma radiosensitivity via NF-ΚB inhibition by suppressing IKKγ expression

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.

Keywords:

• Curcumin
• radiosensitivity
• laryngeal squamous carcinoma
• NF-κB
• IKKγ

Acknowledgments

The authors thank the central laboratory of Taihe hospital for providing laboratory equipment. The authors thank “SAGE Author Services” for language correction.

Funding Sources

This work was supported by the National Natural Science Foundation of China (Nos. 81802997, 81602391, 81502666); The Foundation for Free Exploration of Hubei University of Medicine (FDFR201802); the Natural Science Foundation of Hubei Province of China (Nos. 2019CFA034, 2017CFB167, 2018CFB405, 2017CFB456); the Natural Science Foundation of Hubei Provincial Department of Education (Nos. D20172102, Q20162109) and the Scientific and Technological Project of Shiyan City of Hubei Province (Nos. 19Y40, 16Y19, 17Y10, 17Y12).

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Nos. 81802997, 81602391, and 81502666]; The Foundation for Free Exploration of Hubei University of Medicine [FDFR201802]; the Natural Science Foundation of Hubei Province of China [Nos. 2019CFA034, 2017CFB167, 2018CFB405, and 2017CFB456]; the Natural Science Foundation of Hubei Provincial Department of Education [Nos. D20172102 and Q20162109]; and the Scientific and Technological Project of Shiyan City of Hubei Province [Nos. 19Y40, 16Y19, 17Y10, and 17Y12].