Radioactive 125I Seed Inhibits the Cell Growth, Migration, and Invasion of Nasopharyngeal Carcinoma by Triggering DNA Damage and Inactivating VEGF-A/ERK Signaling

Although radiotherapy technology has progressed rapidly in the past decade, the inefficiency of radiation and cancer cell resistance mean that the 5-year survival rate of patients with nasopharyngeal carcinoma (NPC) is low. Radioactive I-125 seed implantation has received increasing attention as a clinical treatment for cancers. Vascular endothelial growth factor-A (VEGF-A) is one of the most important members of the VEGF family and plays an important role in cell migration through the extracellular-signal-regulated kinase (ERK) pathway. Here we show that radioactive I-125 seeds more effectively inhibit NPC cell growth through DNA damage and subsequent induction of apoptosis, compared with X-ray irradiation. Moreover, cell migration was effectively inhibited by I-125 seed irradiation through VEGF-A/ERK inactivation. VEGF-A pretreatment significantly blocked I-125 seed irradiation-induced inhibition of cell migration by recovering the levels of phosphorylated ERK (p-ERK) protein. Interestingly, in vivo study results confirmed that I-125 seed irradiation was more effective in inhibiting tumor growth than X-ray irradiation. Taken together, these results suggest that radioactive I-125 seeds exert novel anticancer activity by triggering DNA damage and inactivating VEGF-A/ERK signaling. Our finding provides evidence for the efficacy of I-125 seeds for treating NPC patients, especially those with local recurrence.