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HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair

  • Authors:
    • Guohu Han
    • Rui Ling
    • Changchun Sun
    • Xuefeng Wang
    • Yuepeng Zhou
    • Lijiang Yu
    • Shenzha Liu
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Jingjiang People's Hospital, The Seventh Affiliated Hospital of Yangzhou University, Jingjiang, Jiangsu 214500, P.R. China, Department of Oncology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China, Department of Central Laboratory, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China, Department of Nuclear Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China
    Copyright: © Han et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 503
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    Published online on: April 29, 2021
       https://doi.org/10.3892/ol.2021.12764
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Abstract

Radiotherapy is an effective therapeutic strategy in esophageal squamous cell carcinoma (ESCC). However, acquired radioresistance of cancer cells leads to radiotherapy failure. The present study aimed to investigate the mechanisms of the effect of high mobility group box 1 (HMGB1) on the radiation sensitivity of ESCC. Small interfering RNA (si) transfection was used to generate three groups of TE‑1 cells (TE‑1, negative control and TE‑1+siHMGB1), and the protein expression levels of HMGB1 in TE‑1 cells were detected by western blotting. These groups of TE‑1 cells were irradiated with different doses (0, 2, 4, 6 and 8 Gy) of X‑rays after transfection. Subsequently, the viability of TE‑1 cells was detected using an MTT assay, and the survival fraction of TE‑1 cells was observed using a colony formation assay. The apoptotic rate, reactive oxygen species (ROS) content and levels of phosphorylated (p)‑histone H2AX at S139 (p‑γH2AX) of the cells were detected by flow cytometry. The alterations in mRNA expression levels of nicotinamide adenine nucleotide phosphate oxidase (NOX)1 and NOX5 were detected by reverse transcription‑quantitative PCR, while the changes in protein levels of caspase‑3, poly(ADP‑ribose) polymerase, p‑p38, p‑ERK1/2 and p‑JNK were detected by western blotting. The results revealed that HMGB1 knockdown significantly decreased cell viability, and the apoptosis rate of TE‑1 cells transfected with siHMGB1 combined with radiation treatment was increased compared with that in cells with either siHMGB1 transfection or radiation treatment alone. HMGB1 knockdown increased nicotinamide adenine nucleotide phosphate oxidase‑mediated ROS production and induced DNA damage via the MAPK signaling pathway, which may promote apoptosis and radiosensitivity after radiation in TE‑1 cells. In conclusion, targeting HMGB1 may represent a promising strategy to increase the efficacy of radiation therapy for ESCC.
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Copy and paste a formatted citation
Spandidos Publications style
Han G, Ling R, Sun C, Wang X, Zhou Y, Yu L and Liu S: HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair. Oncol Lett 22: 503, 2021.
APA
Han, G., Ling, R., Sun, C., Wang, X., Zhou, Y., Yu, L., & Liu, S. (2021). HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair. Oncology Letters, 22, 503. https://doi.org/10.3892/ol.2021.12764
MLA
Han, G., Ling, R., Sun, C., Wang, X., Zhou, Y., Yu, L., Liu, S."HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair". Oncology Letters 22.1 (2021): 503.
Chicago
Han, G., Ling, R., Sun, C., Wang, X., Zhou, Y., Yu, L., Liu, S."HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair". Oncology Letters 22, no. 1 (2021): 503. https://doi.org/10.3892/ol.2021.12764
Copy and paste a formatted citation
x
Spandidos Publications style
Han G, Ling R, Sun C, Wang X, Zhou Y, Yu L and Liu S: HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair. Oncol Lett 22: 503, 2021.
APA
Han, G., Ling, R., Sun, C., Wang, X., Zhou, Y., Yu, L., & Liu, S. (2021). HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair. Oncology Letters, 22, 503. https://doi.org/10.3892/ol.2021.12764
MLA
Han, G., Ling, R., Sun, C., Wang, X., Zhou, Y., Yu, L., Liu, S."HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair". Oncology Letters 22.1 (2021): 503.
Chicago
Han, G., Ling, R., Sun, C., Wang, X., Zhou, Y., Yu, L., Liu, S."HMGB1 knockdown increases the radiosensitivity of esophageal squamous cell carcinoma by regulating the expression of molecules involved in DNA repair". Oncology Letters 22, no. 1 (2021): 503. https://doi.org/10.3892/ol.2021.12764
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