Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells

I. Tsang Chiang, Yu Chang Liu, Wei Hsun Wang, Fei Ting Hsu, Hong Wen Chen, Wuu Jyh Lin, Wen Yi Chang, Jeng Jong Hwang

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Invasion by hepatocellular carcinoma (HCC) has been reported to occur via the up-regulation of nuclear factorkappaB (NF-κB). Sorafenib can improve the overall survival in patients with HCC, however, the association of its inhibitory mechanisms with the inactivation of NF-κB remains unclear. Here, Huh7 cell line transfected with NF-κB-luc2 vector was used to study the effects of sorafenib on NF-κB activity, on expressions of matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF), which were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). TPA increased the NF-κB activity and the expressions of MMP-9 and VEGF significantly, but its effects were suppressed by sorafenib in a dose-dependent manner. Similar results were found with PD98059, an inhibitor of extracellular signalregulated kinase (ERK). Furthermore, transfection of Huh7 cell with an inhibitor of kappaB-α mutant vector, led to reduced TPA-induced MMP-9 and VEGF mRNA expressions. Sorafenib inhibits TPA-induced MMP-9 and VEGF expressions via the suppression of ERK/NF-κB pathway in HCC cells.

Original languageEnglish
Pages (from-to)671-682
Number of pages12
JournalIn Vivo
Volume26
Issue number4
Publication statusPublished - Jul 2012
Externally publishedYes

Keywords

  • Hepatocellular carcinoma
  • Huh 7 cells
  • MMP-9
  • NF-κB
  • Sorafenib
  • VEGF

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology

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    Chiang, I. T., Liu, Y. C., Wang, W. H., Hsu, F. T., Chen, H. W., Lin, W. J., Chang, W. Y., & Hwang, J. J. (2012). Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK/NF-κB pathway in hepatocellular carcinoma cells. In Vivo, 26(4), 671-682.