title: Bacitracin Inhibits the Migration of U87-MG Glioma Cells via Interferences of the Integrin Outside-in Signaling Pathway.
abstract: OBJECTIVE
  Protein disulfide isomerase (PDI) acts as a chaperone on the cell surface, and it has been reported that PDI is associated with the tumor cell migration and invasion. The aims of this study are to investigate the anti-migration effect of bacitracin, which is an inhibitor of PDI, and the associated factor in this process.
  
  
  METHODS
  U87-MG glioma cells were treated with bacitracin in 1.25, 2.5, 3.75, and 5.0 mM concentrations. Western blot with caspase-3 was applied to evaluate the cytotoxicity of bacitracin. Adhesion, morphology, migration assays, and organotypic brain-slice culture were performed to evaluate the effect of bacitracin to the tumor cell. Western blot, PCR, and gelatin zymography were performed to investigate the associated factors. Thirty glioma tissues were collected following immunohistochemistry and Western blot.
  
  
  RESULTS
  Bacitracin showed a cytotoxicity in 3rd (p<0.05) and 4th (p<0.001) days, in 5.0 Mm concentration. The cell adhesion significantly decreased and the cells became a round shape after treated with bacitracin. The migration ability, the expression of phosphorylated focal adhesion kinase (p-FAK) and matrix metalloproteinase-2 (MMP-2) decreased in a bacitracin dose- and time-dependent manner. The U87-MG cells exhibited low-invasiveness in the 2.5 mM, compared with the untreated in organotypic brain-slice culture. PDI was expressed in the tumor margin, and significantly increased with histological glioma grades (p<0.001).
  
  
  CONCLUSIONS
  Bacitracin, as a functional inhibitor of PDI, decreased the phosphorylated FAK and the secreted MMP-2, which are the downstream of integrin and play a major role in cell migration and invasion, might become one of the feasible therapeutic strategies for glioblastoma.
authors.affiliation: Brain Tumor Research Laboratory and Department of Neurosurgery Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hopital and Medical School, Hwasun, Korea.
authors.forename: Songyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Brain Tumor Research Laboratory and Department of Neurosurgery Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hopital and Medical School, Hwasun, Korea.
authors.forename: Chunhao
authors.initials: C
authors.lastname: Li
authors.affiliation: Brain Tumor Research Laboratory and Department of Neurosurgery Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hopital and Medical School, Hwasun, Korea.
authors.forename: Hyang-Hwa
authors.initials: HH
authors.lastname: Ryu
authors.affiliation: Brain Tumor Research Laboratory and Department of Neurosurgery Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hopital and Medical School, Hwasun, Korea.
authors.forename: Sa-Hoe
authors.initials: SH
authors.lastname: Lim
authors.affiliation: Brain Tumor Research Laboratory and Department of Neurosurgery Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hopital and Medical School, Hwasun, Korea.
authors.forename: Woo-Youl
authors.initials: WY
authors.lastname: Jang
authors.affiliation: Brain Tumor Research Laboratory and Department of Neurosurgery Chonnam National University Research Institute of Medical Sciences, Chonnam National University Hwasun Hopital and Medical School, Hwasun, Korea.
authors.forename: Shin
authors.initials: S
authors.lastname: Jung
keywords: Bacitracin; Glioma; Integrin; Invasion; Migration; Protein disulfide isomerase