Radiosensitizing effects of c‑myc gene knockdown‑induced G2/M phase arrest by intrinsic stimuli via the mitochondrial signaling pathway

Fan,Yunpeng; Jia,Xiaofeng; Xie,Tao; Zhu,Liulong; He,Fan

doi:10.3892/or.2020.7806

Radiosensitizing effects of c‑myc gene knockdown‑induced G2/M phase arrest by intrinsic stimuli via the mitochondrial signaling pathway

Authors:
- Yunpeng Fan
- Xiaofeng Jia
- Tao Xie
- Liulong Zhu
- Fan He
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Affiliations: The Affiliated Hangzhou Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China, College of Life Science, China Jiliang University, Hangzhou, Zhejiang 310018, P.R. China, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R. China
Published online on: October 13, 2020 https://doi.org/10.3892/or.2020.7806
Pages: 2669-2677
Copyright: © Fan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and adolescents and its long‑term survival rate has stagnated in the past decades. Previous studies have shown that tumors in the G2/M phase are more sensitive to radiotherapy. The proto‑oncogene c‑myc is a transformed member of the myc family and c‑myc‑interacting zinc finger protein‑1 (Miz‑1) is a poly‑Cys2His2 zinc finger (ZF) activator of cell cycle regulator genes, such as the cyclin‑dependent kinase inhibitor p21. C‑myc can repress the expression of p21 by binding to Miz‑1 and abolishing the interaction between Miz‑1 and its co‑activators, which induces G2/M phase arrest. Therefore, the present study investigated the radiosensitizing effects of the c‑myc gene and the sensitizing apoptosis pathway, aiming to identify a more effective combination radiotherapy treatment for osteosarcoma. The present study demonstrated that the c‑myc gene was overexpressed in osteosarcoma cells compared to osteoblasts. Following inhibition of c‑myc gene expression in osteosarcoma cells, tumor proliferation was significantly hindered after inducing G2/M phase arrest via regulating G2/M phase‑associated proteins. Additionally, it was revealed that inhibiting c‑myc gene expression combined with radiotherapy could significantly increase the apoptosis rate of osteosarcoma cells via the mitochondrial signaling pathway. In summary, the present study verified the radiosensitizing effects of c‑myc gene knockdown‑induced G2/M phase arrest, which was achieved by intrinsic stimuli through the mitochondrial signaling pathway.

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