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Salinomycin inhibits hepatocellular carcinoma cell invasion and migration through JNK/JunD pathway-mediated MMP9

Ling Xu1, Ting Wang1, Wen-Ying Meng1

  • 1Department of Gastroenterology, Shanghai Tongren Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200336, P.R. China.

Oncology Reports
|December 20, 2014
PubMed

Insights

Salinomycin (Salin) reduces hepatocellular carcinoma (HCC) cell migration and invasion by inhibiting MMP9 expression. This antitumor effect involves the c-Jun NH2-kinase (JNK) pathway and JunD protein.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Salinomycin (Salin) shows potential as an antitumor drug for solid tumors.
  • The impact of Salin on hepatocellular carcinoma (HCC) cell migration and invasion remains largely uncharacterized.
  • Understanding Salin's mechanism in HCC is crucial for its therapeutic development.

Purpose of the Study:

  • To investigate the antitumor efficacy of Salin in hepatocellular carcinoma (HCC) cells.
  • To elucidate the underlying molecular mechanisms by which Salin affects HCC cell behavior.

Main Methods:

  • Human HCCLM3 cells were treated with varying concentrations of Salin.
  • Cell migration and invasion assays were performed.
  • MMP9 expression, promoter activity, and the AP-1 signaling pathway (including JunD and JNK phosphorylation) were analyzed.

Main Results:

  • Salin significantly reduced HCCLM3 cell migration and invasion in a dose-dependent manner.
  • This reduction was correlated with decreased matrix metalloproteinase 9 (MMP9) expression.
  • Salin modulated MMP9 expression via the AP-1 site in the MMP9 enhancer, decreasing JunD levels and increasing JNK phosphorylation.

Conclusions:

  • Salin exhibits antitumor effects against HCC cells by inhibiting migration and invasion.
  • The c-Jun NH2-kinase (JNK) signaling pathway and JunD appear to mediate Salin's regulation of MMP9 expression in HCC.
  • These findings offer new insights into Salin's therapeutic potential for HCC.

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