Acetaldehyde induces matrix metalloproteinase-9 gene expression via nuclear factor-kappa B and activator protein 1 signaling pathways in human hepatocellular carcinoma cells: Association with the invasive potential

作者：Hsiang Chien Yun^*; Wu Shih Lu; Chen Jaw Chyun; Lo Hsin Yi; Li Chia Cheng; Chiang Su Yin; Wu Hsiu Ching; Ho Tin Yun

来源：Toxicology Letters, 2007, 171(1-2): 78-86.

DOI：10.1016/j.toxlet.2007.04.009

• acetaldehyde
• matrix metalloproteinase-9
• tumor invasion
• nuclear factor-kappa B
• activator protein 1

Alcohol consumption is a significant risk factor for hepatocellular carcinoma (HCC). Alcohol also increases the prevalence of invasion in HCC patients. However, the molecular mechanism on the metastatic effect of alcohol is unclear so far. Herein we demonstrated that acetaldehyde, the primary metabolite of ethanol, increased matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and promoted cell invasion through the up-regulation of MMP-9 gene transcription in HepG2 cells. The transcription of MMP-9 gene was regulated by 10 mu M acetaldehyde via inductions of nuclear factor-kappa B (NF-kappa B) and activator protein 1 (AP-1) activities. Acetaldehyde stimulated the translocation of NF-kappa B into nucleus through inhibitory kappa B-alpha (I kappa B-alpha) and c-Jun N-terminal kinase (JNK)/beta-transducin repeat-containing protein (P-TrCP) signaling pathways. Acetaldehyde also induced AP-1 activity via the phosphorylation of p38 kinase. In conclusion, our findings demonstrated for the first time that acetaldehyde activated NF-kappa B and AP-1 activities via I kappa B, JNK/beta-TrCP, and p38 signaling pathways, resulting in MMP-9 gene expression and hepatocarcinoma cells invasion. These results suggested that acetaldehyde might be a potential factor involved in the invasiveness of HCC in alcoholic patients.

• 出版日期2007-6-15
• 单位中国医科大学