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NF-kappaB inhibition in human hepatocellular carcinoma and its potential as adjunct to sorafenib based therapy.

Abstract：

:Nuclear factor-kappaB (NF-kappaB) has been shown to play an important role in the development and progression of cancer. In this study, we systematically examined NF-kappaBp65 signaling pathway in both human hepatocellular carcinoma (HCC) tissue and HCC cell lines. NF-kappaBp65 signaling pathway is aberrantly expressed and activated in both human HCC tissue and HCC Hep3B cells. Inhibition of NF-kappaB activity significantly reduced proliferation and invasion of Hep3B cells as well as down-regulated the expression of invasion-related molecules including matrix metalloproteinase (MMP)-2, MMP-9, membrane type-1 MMP (MT1-MMP), urokinase plasminogen activator (uPA) and vascular endothelial growth factor (VEGF). Hep3B cells exhibited a dose-dependent increase in apoptosis after receiving sorafenib treatment. Inhibition of NF-kappaB activity strongly sensitized Hep3B cells to sorafenib-induced cell death. Mechanistically, combined treatment of sorafenib and NF-kappaB inhibition enhanced inhibition of MAPK signaling and down-regulation of anti-apoptotic protein Mcl-1 expression. These observations indicate that inhibition of NF-kappaB may be a potential antineoplastic therapy for HCC, especially the combination of NF-kappaB inhibition and sorafenib provides a novel therapeutic strategy for patients with advanced-stage HCC.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Wu JM,Sheng H,Saxena R,Skill NJ,Bhat-Nakshatri P,Yu M,Nakshatri H,Maluccio MA

doi

10.1016/j.canlet.2008.12.031

subject

Has Abstract

pub_date

2009-06-18 00:00:00

pages

145-155

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(09)00005-6

journal_volume

278

pub_type

杂志文章

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