Radioactive (125)I seeds inhibit cell growth and epithelial-mesenchymal transition in human glioblastoma multiforme via a ROS-mediated signaling pathway

BMC Cancer. 2015 Feb 19;15:1. doi: 10.1186/1471-2407-15-1.

Abstract

Background: Glioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm in adults. Radioactive (125)I seed implantation has been widely applied in the treatment of cancers. Moreover, previous clinical trials have confirmed that (125)I seeds treatment was an effective therapy in GBM. We sought to investigate the effect of (125)I seed on GBM cell growth and Epithelial-mesenchymal transition (EMT).

Methods: Cells were exposed to irradiation at different doses. Colony-formation assay, EdU assay, cell cycle analysis, and TUNEL assay were preformed to investigate the radiation sensitivity. The effects of (125)I seeds irradiation on EMT were measured by transwell, Boyden and wound-healing assays. The levels of reactive oxygen species (ROS) were measured by DCF-DA assay. Moreover, the radiation sensitivity and EMT were investigated with or without pretreatment with glutathione. Additionally, nude mice with tumors were measured after treated with radiation.

Results: Radioactive (125)I seeds are more effective than X-ray irradiation in inhibiting GBM cell growth. Moreover, EMT was effectively inhibited by (125)I seed irradiation. A mechanism study indicated that GBM cell growth and EMT inhibition were induced by (125)I seeds with the involvement of a ROS-mediated signaling pathway.

Conclusions: Radioactive (125)I seeds exhibit novel anticancer activity via a ROS-mediated signaling pathway. These findings have clinical implications for the treatment of patients with GBM by (125)I seeds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Neoplasms / pathology
  • Brain Neoplasms / radiotherapy*
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • G2 Phase Cell Cycle Checkpoints
  • Glioblastoma / pathology
  • Glioblastoma / radiotherapy*
  • Humans
  • Iodine Radioisotopes / pharmacology*
  • Iodine Radioisotopes / therapeutic use
  • Mice, Inbred BALB C
  • Mice, Nude
  • Radiation Tolerance
  • Radiopharmaceuticals / pharmacology*
  • Radiopharmaceuticals / therapeutic use
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • Xenograft Model Antitumor Assays

Substances

  • Iodine Radioisotopes
  • Radiopharmaceuticals
  • Reactive Oxygen Species