Expressions of HMGB1, MMP-2 and MMP-9 and prognostic alue in human laryngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expressions of high mobility group box B1 protein (HMGB1), matrix metalloproteinases-2(MMP-2) and matrix metalloproteinases-9 (MMP-9) in human laryngeal carcinoma and study their relationships with clinicopathological characteristics and prognosis.@*METHOD@#The expressions of HMGB1, MMP-2 and MMP-9 proteins were examined with the EnVision immunohistochemical method in 61 cases of laryngeal carcinoma. The expressions of HMGB1, MMP-2 and MMP-9 mRNA were detected by real-time quantitative RT-PCR method in 30 cases of laryngeal carcinoma.@*RESULT@#The positive expression rates of HMGB1, MMP-2 and MMP-9 proteins were significantly higher in laryngeal carcinoma than those in adjacent tissue (chi2=44.934, 49.923 and 36.054, P<0.01). The relative expression levels of HMGB1, MMP-2 and MMP-9 mRNA in laryngeal carcinoma were significantly higher than those in adjacent tissue (t=5.940, 7.005 and 7.664, P<0.01). The high level expression of HMGB1, MMP-2, MMP-9 proteins was closely associated with T stage, clinical stage and the status of lymph node metastasis (P<0.05 or P<0.01). There was a positive correlation between the expression of HMGB1 and MMP-9 protein (r=0.381, P<0.01). Univariate analysis indicated that the overall survival rate was lower in patients with a positive expression of HMGB1 and MMP-9 than those with negative expression (chi2= 4.974, 6.418, P<0.05). Multivariate analysis showed that HMGB1 was a risk predictor. A higher expression of HMGB1 was associated with a shorter survival time.@*CONCLUSION@#HMGB1, MMP-2 and MMP-9 play a role in invasion and metastasis of laryngeal carcinoma; Also there is a synergistic effect between HMGB1 and MMP-9; Moreover HMGB1 may be a independent prognostic factor.

Effect of MAPK/NF-kappaB signaling pathway on extracellular release of HMGB1 induced by hypoxia in laryngeal Hep-2 carcinoma cells / 临床耳鼻咽喉头颈外科杂志

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.