Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice

Mao Chi Weng, Mei Hui Wang, Jai Jen Tsai, Yu Cheng Kuo, Yu Chang Liu, Fei Ting Hsu, Hsin Ell Wang

Research output: Contribution to journalArticle

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Abstract

Regorafenib has been demonstrated in our previous study to trigger apoptosis through suppression of extracellular signal-regulated kinase (ERK)/nuclear factor-κB (NF-κB) activation in hepatocellular carcinoma (HCC) SK-Hep1 cells in vitro. However, the effect of regorafenib on NF-κB-modulated tumor progression in HCC in vivo is ambiguous. The aim of the present study is to investigate the effect of regorafenib on NF-κB-modulated tumor progression in HCC bearing mouse model. pGL4.50 luciferase reporter vector transfected SK-Hep1 (SK-Hep1/luc2) and Hep3B 2.1-7 tumor bearing mice were established and used for the present study. Mice were treated with vehicle or regorafenib (20 mg/kg/day by gavage) for 14 days. Effects of regorafenib on tumor growth and protein expression together with toxicity of regorafenib were evaluated with digital caliper and bioluminescence imaging (BLI), ex vivo Western blotting immunohistochemistry (IHC) staining, and measurement of body weight and pathological examination of liver tissue, respectively, in SK-Hep1/luc2 and Hep3B 2.1-7 tumor bearing mice. The results indicated regorafenib significantly reduced tumor growth and expression of phosphorylated ERK, NF-κB p65 (Ser536), phosphorylated AKT, and tumor progression-associated proteins. In addition, we found regorafenib induced both extrinsic and intrinsic apoptotic pathways. Body weight and liver morphology were not affected by regorafenib treatment. Our findings present the mechanism of tumor progression inhibition by regorafenib is linked to suppression of ERK/NF-κB signaling in SK-Hep1/luc2 and Hep3B 2.1-7 tumor bearing mice.

Original languageEnglish
Article numberBSR20171264
JournalBioscience Reports
Volume38
Issue number3
DOIs
Publication statusPublished - May 8 2018

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Bearings (structural)
Extracellular Signal-Regulated MAP Kinases
Tumors
Hepatocellular Carcinoma
Chemical activation
Neoplasms
Liver
Body Weight
regorafenib
Bioluminescence
Growth
Luciferases
Toxicity
Proteins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Weng, M. C., Wang, M. H., Tsai, J. J., Kuo, Y. C., Liu, Y. C., Hsu, F. T., & Wang, H. E. (2018). Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice. Bioscience Reports, 38(3), [BSR20171264]. https://doi.org/10.1042/BSR20171264

Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice. / Weng, Mao Chi; Wang, Mei Hui; Tsai, Jai Jen; Kuo, Yu Cheng; Liu, Yu Chang; Hsu, Fei Ting; Wang, Hsin Ell.

In: Bioscience Reports, Vol. 38, No. 3, BSR20171264, 08.05.2018.

Research output: Contribution to journalArticle

Weng, Mao Chi ; Wang, Mei Hui ; Tsai, Jai Jen ; Kuo, Yu Cheng ; Liu, Yu Chang ; Hsu, Fei Ting ; Wang, Hsin Ell. / Regorafenib inhibits tumor progression through suppression of ERK/NF-κB activation in hepatocellular carcinoma bearing mice. In: Bioscience Reports. 2018 ; Vol. 38, No. 3.
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