Radioactive ¹²⁵I seed inhibits the cell growth, migration, and invasion of nasopharyngeal carcinoma by triggering DNA damage and inactivating VEGF-A/ERK signaling

PLoS One. 2013 Sep 10;8(9):e74038. doi: 10.1371/journal.pone.0074038. eCollection 2013.

Abstract

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 (125)I 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 (125)I 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 (125)I seed irradiation through VEGF-A/ERK inactivation. VEGF-A pretreatment significantly blocked (125)I seed irradiation-induced inhibition of cell migration by recovering the levels of phosphorylated ERK (p-ERK) protein. Interestingly, in vivo study results confirmed that (125)I seed irradiation was more effective in inhibiting tumor growth than X-ray irradiation. Taken together, these results suggest that radioactive (125)I seeds exert novel anticancer activity by triggering DNA damage and inactivating VEGF-A/ERK signaling. Our finding provides evidence for the efficacy of (125)I seeds for treating NPC patients, especially those with local recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Carcinoma
  • Cell Cycle Checkpoints / radiation effects
  • Cell Line, Tumor
  • Cell Movement / radiation effects
  • Cell Proliferation / radiation effects
  • DNA Damage / radiation effects*
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Female
  • Humans
  • Iodine Radioisotopes / administration & dosage*
  • Mice
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / genetics*
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / radiotherapy
  • Neoplasm Invasiveness
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / radiation effects*
  • Tumor Burden / radiation effects
  • Vascular Endothelial Growth Factor A / metabolism*
  • X-Rays
  • Xenograft Model Antitumor Assays

Substances

  • Iodine Radioisotopes
  • Reactive Oxygen Species
  • Vascular Endothelial Growth Factor A
  • Extracellular Signal-Regulated MAP Kinases

Grants and funding

This study was supported by the National Natural Science Foundation of China-Guangdong Joint Fund (u0732006), National Science and Technology support program, Natural Science Foundation of China and Program for New Century Excellent Talents in University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.