Regorafenib diminishes the expression and secretion of angiogenesis and metastasis associated proteins and inhibits cell invasion via NF-κB inactivation in SK-Hep1 cells

Liu,Yu‑Chang; Wu,Reng‑Hong; Wang,Wei‑Shu

doi:10.3892/ol.2017.6142

Regorafenib diminishes the expression and secretion of angiogenesis and metastasis associated proteins and inhibits cell invasion via NF-κB inactivation in SK-Hep1 cells

Authors:
- Yu‑Chang Liu
- Reng‑Hong Wu
- Wei‑Shu Wang
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Affiliations: Department of Radiation Oncology, National Yang‑Ming University Hospital, Yilan 260, Taiwan, R.O.C., Department of Radiological Technology, Central Taiwan University of Science and Technology, Taichung 40601, Taiwan, R.O.C., Faculty of Medicine, National Yang‑Ming University School of Medicine, Taipei 112, Taiwan, R.O.C.
Published online on: May 9, 2017 https://doi.org/10.3892/ol.2017.6142
Pages: 461-467

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Abstract

The aim of the present study was to investigate the effects of regorafenib on the nuclear factor κ‑light‑chain‑enhancer of activated B cells (NF)‑κB‑modulated expression of angiogenesis‑ and metastasis‑associated proteins and cell invasion in human hepatocellular carcinoma SK‑Hep1 cells. The SK‑Hep1 cells were treated with different concentrations of NF‑κB inhibitor 4‑N‑[2‑(4‑phenoxyphenyl) ethyl] quinazoline‑4,6‑diamine (QNZ) or regorafenib for 24 or 48 h. The effects of QNZ and regorafenib on cell viability, NF‑κB activation, expression and secretion levels of angiogenesis‑ and metastasis‑associated proteins and cell invasion were evaluated with MTT assays, western blotting, ELISA, gelatin zymography and cell invasion assays. The results demonstrated that QNZ and regorafenib significantly reduced the expression and secretion levels of the angiogenesis‑ and metastasis‑associated proteins vascular endothelial growth factor, tumor necrosis factor‑α, interleukin (IL)‑1β, IL‑6, matrix metalloproteinase (MMP)‑2 and MMP‑9, NF‑κB activation and cell invasion. In conclusion, the inhibition of NF‑κB activation induces anti‑angiogenic and antimetastatic effects in SK‑Hep1 cells. Regorafenib reduces the level of expression and secretion of angiogenesis‑ and metastasis‑associated proteins and cell invasion through the suppression of NF‑κB activation in SK‑Hep1 cells.

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