Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells

Ma,Tao; Guo,Rui; Wang,Xi; Shen,Wen-Tong; Zhu,Min; Jin,Ye-Ning; Xu,Hao-Ping

doi:10.3892/ol.2020.12328

Lentiviral vector with a radiation‑inducible promoter, carrying the ING4 gene, mediates radiosensitization controlled by radiotherapy in cervical cancer cells

Authors:
- Tao Ma
- Rui Guo
- Xi Wang
- Wen-Tong Shen
- Min Zhu
- Ye-Ning Jin
- Hao-Ping Xu
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Affiliations: Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China, Department of Neurology, Hackensack Meridian Health JFK Medical Center, Edison, NJ 08820, USA
Published online on: November 25, 2020 https://doi.org/10.3892/ol.2020.12328
Article Number: 67
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The presence of hypoxia in solid tumors is considered one of the major factors that contribute to radiation resistance. The aim of the present study was to establish a therapeutic system, which can be controlled by radiation itself, to enhance radiosensitivity. For this purpose, a lentiviral gene therapy vector containing the human inhibitor of growth 4 (ING4) and its upstream promoter, human early growth response factor‑1 (EGR1), which possesses the radiation‑inducible characteristics to activate the transcription of its downstream genes, was constructed. Downstream fluorescence proteins were investigated to ensure that the EGR1 promoter was induced by irradiation. Furthermore, ING4 open reading frame (ORF) expression was detected by western blotting. The cell cycle was analyzed by fluorescence‑activated cell sorting analysis 48 h after the cells were exposed to X‑rays ranging between 0 and 8 Gy. In cells stably and transiently transfected with reporter plasmids, the EGR1‑driver gene was sensitive to ionizing irradiation. Furthermore, irradiation‑induced ING4 gene expression was observed. The enhanced ING4 expression increased the number of cells in the G₂/M phase and decreased the proportion of cells in the G₁/S phase. Therefore, ING4 expression inhibited cell proliferation and was associated with less colonies being formed. Furthermore, ING4 suppressed hypoxia‑inducible factor 1α expression under hypoxic conditions and promoted cell apoptosis. Overall, these results revealed that combining the EGR1 promoter and ING4 ORF using a lentivirus system may be a promising therapeutic strategy with which to enhance radiosensitivity controlled by radiation. However, further studies using in vivo models are required to confirm these findings.

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