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.
Oncol Rep. 2020 Dec;44(6):2669-2677. doi: 10.3892/or.2020.7806. Epub 2020 Oct 13.
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.
骨肉瘤是儿童和青少年中最常见的原发性恶性骨肿瘤，其长期生存率在过去几十年中一直停滞不前。先前的研究表明，G2/M 期的肿瘤对放疗更敏感。原癌基因 c-myc 是 myc 家族的转化成员，c-myc 相互作用锌指蛋白-1（Miz-1）是细胞周期调节剂基因的多-Cys2His2 锌指（ZF）激活剂，如细胞周期蛋白依赖性激酶抑制剂 p21。c-myc 可以通过与 Miz-1 结合并消除 Miz-1 与其共激活剂之间的相互作用来抑制 p21 的表达，从而诱导 G2/M 期阻滞。因此，本研究探讨了 c-myc 基因的放射增敏作用和敏感凋亡途径，旨在为骨肉瘤确定更有效的联合放疗治疗方法。本研究表明，与成骨细胞相比，骨肉瘤细胞中 c-myc 基因过度表达。在骨肉瘤细胞中抑制 c-myc 基因表达后，通过调节 G2/M 期相关蛋白诱导 G2/M 期阻滞，显著抑制肿瘤增殖。此外，研究还揭示了抑制 c-myc 基因表达与放疗相结合，通过线粒体信号通路，可显著增加骨肉瘤细胞的凋亡率。综上所述，本研究验证了 c-myc 基因敲低诱导的 G2/M 期阻滞的放射增敏作用，该作用是通过线粒体信号通路通过内在刺激实现的。
