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

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

In Vivo. 2012 Jul-Aug;26(4):671-81.

Authors

I-Tsang Chiang¹, Yu-Chang Liu, Wei-Hsun Wang, Fei-Ting Hsu, Hong-Wen Chen, Wuu-Jyh Lin, Wen-Yi Chang, Jeng-Jong Hwang

Affiliation

¹ Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, and Department of Radiation Oncology and Hospice Care Center, Mackay Memorial Hospital, No. 155, Sec. 2, Li-Nong St., Bei-tou, Taipei 112, Taiwan, ROC.

PMID: 22773582

Abstract

Invasion by hepatocellular carcinoma (HCC) has been reported to occur via the up-regulation of nuclear factor-kappaB (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 signal-regulated 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Benzenesulfonates / pharmacology*
Carcinoma, Hepatocellular / enzymology
Carcinoma, Hepatocellular / metabolism*
Carcinoma, Hepatocellular / pathology
Cell Line, Tumor
DNA Primers
Electrophoretic Mobility Shift Assay
Extracellular Signal-Regulated MAP Kinases / metabolism*
Humans
Liver Neoplasms / enzymology
Liver Neoplasms / metabolism*
Liver Neoplasms / pathology
Matrix Metalloproteinase 9 / drug effects*
Matrix Metalloproteinase 9 / metabolism
NF-kappa B / metabolism*
Niacinamide / analogs & derivatives
Phenylurea Compounds
Pyridines / pharmacology*
Reverse Transcriptase Polymerase Chain Reaction
Sorafenib
Tetradecanoylphorbol Acetate / pharmacology*
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Vascular Endothelial Growth Factor A / metabolism

Substances

Benzenesulfonates
DNA Primers
NF-kappa B
Phenylurea Compounds
Pyridines
Vascular Endothelial Growth Factor A
Niacinamide
Sorafenib
Extracellular Signal-Regulated MAP Kinases
Matrix Metalloproteinase 9
Tetradecanoylphorbol Acetate