[Effect of MAPK/NF-kappaB signaling pathway on extracellular release of HMGB1 induced by hypoxia in laryngeal Hep-2 carcinoma cells]

Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2013 Oct;27(19):1076-9.
[Article in Chinese]

Abstract

Objective: To investigate the extracellular release of high mobility group box 1 (HMGB1) in laryngeal Hep-2 carcinoma cells induced by hypoxia and its possible mechanism.

Method: The changes of HMGB1 concentration in the culture medium as well as HMGB1 protein and mRNA expression in Hep-2 cells were investigated after the cells were cultured with 1% O2 for different durations. Inhibitory effects of MAPK pathway inhibitors (PD98059. SP600125, and SB202190) and nuclear NF-kappaB pathway inhibitor (PDTC) with various concentrations on extracellular HMGB1 release were observed in hypoxia-induced Hep-2 cells. The HMGB1 concentration and HMGB1 protein expression were measured by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. The HMGB1 mRNA expression was determined by real-time quantitative PCR(RT-PCR).

Result: The HMGB1 concentration in the culture medium and the HMGB1 protein expression in Hep-2 cells increased after the cells were subjected to hypoxia culture for 12 h in a time-dependent manner. The level of HMGB1 mRNA expression in Hep-2 cells increased after the cells were induced by hypoxia for 6h PD98059 and SP600125 with 20 micromol/ L and PDTC with 50 mg/L partly inhibited extracellular release of HMGB1 in hypoxia-cultured Hcp-2 cells.

Conclusion: Hypoxia induces laryngeal carcinoma cells to release HMGH1. which may be related to MAPK/NF-kappaB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes
  • Cell Hypoxia
  • Cell Line, Tumor
  • Flavonoids
  • HMGB1 Protein / metabolism*
  • Humans
  • Imidazoles
  • MAP Kinase Signaling System*
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism*
  • Protein Kinase Inhibitors
  • Pyridines
  • Pyrrolidines
  • RNA, Messenger / genetics
  • Thiocarbamates

Substances

  • Anthracenes
  • Flavonoids
  • HMGB1 Protein
  • HMGB1 protein, human
  • Imidazoles
  • NF-kappa B
  • Protein Kinase Inhibitors
  • Pyridines
  • Pyrrolidines
  • RNA, Messenger
  • Thiocarbamates
  • pyrazolanthrone
  • pyrrolidine dithiocarbamic acid
  • 4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one