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

Abstract

BackgroundGlioblastoma multiforme (GBM) is the most common primary central nervous system neoplasm in adults. Radioactive 125I seed implantation has been widely applied in the treatment of cancers. Moreover, previous clinical trials have confirmed that 125I seeds treatment was an effective therapy in GBM. We sought to investigate the effect of 125I seed on GBM cell growth and Epithelial-mesenchymal transition (EMT).MethodsCells 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 125I 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.ResultsRadioactive 125I seeds are more effective than X-ray irradiation in inhibiting GBM cell growth. Moreover, EMT was effectively inhibited by 125I seed irradiation. A mechanism study indicated that GBM cell growth and EMT inhibition were induced by 125I seeds with the involvement of a ROS-mediated signaling pathway.ConclusionsRadioactive 125I seeds exhibit novel anticancer activity via a ROS-mediated signaling pathway. These findings have clinical implications for the treatment of patients with GBM by 125I seeds.

Genetics and metabolic deregulation following cancer initiation: A world to explore

“…In this sense, studies performed with NHEK (normal human epidermal keratinocytes) cultivated in medium supplemented with hydrogen peroxide in intervals of 0-72 h showed that ROS induce EMT [65]. Other study, using multiple glioblastoma cells pointed out reduction in E-cadherin level expression and increasing in vimentin, actions observed during EMT [51]. These results demonstrate that cell culture systems are useful models for study EMT, once they mimic faithfully the natural history of the oncogenic process.…”

“…1) [46][47][48][49][50]. For this reason, cells in EMT are resistant to chemotherapies and adjuvant drugs employed in cancer treatment [41,51].…”

“…EMT is crucial along the embryogenesis [44,51,54]. During gastrulation, EMT gives rise to mesoderm, responsible for muscle, bone and connective tissues formation [55].…”

Risk factors for cryptorchidism

“…Berkowitz and Lapinski 94 observed that maternal ‘drug abuse’ had no effect on cryptorchidism risk. While marijuana use by males has been reported to be associated with testicular cancer, 128–131 there have been no studies to date examining maternal use of marijuana and cryptorchidism.…”

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“…They demonstrated that the expression of the epithelial marker EpCAM decreased in migratory cells compared to those remaining in the spheroid, indicating that cells had undergone EMT, as occurs in vivo . Similarly, the transition of breast cancer cells to an invasive phenotype was shown to lead to collagen remodeling and was promoted by human mammary fibroblasts[107, 108]. Other microfluidic studies have shown that invasion of single cancer cell lines into hydrogels increases with increasing metastatic potential[16], either under hypoxia[109] or in the presence of C-X-C motif chemokine 12 (CXCL12) or matrix metalloproteinases (MMP) inhibitors[16].…”