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

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.