Synergistic effect of sorafenib and vitamin K on suppression of hepatocellular carcinoma cell migration and metastasis

Vitamin K plays a role in controlling cell growth. Anti-angiogenic effects of sorafenib lead to impairment of vitamin K uptake and induction of des-γ-carboxyprothrombin release by hepatocellular carcinoma (HCC) cells. We examined sorafenib and vitamin K individually and in combination regarding thei...

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Published in:Anticancer research 2015-04, Vol.35 (4), p.1985-1995
Main Authors: Ha, Tae-Yong, Hwang, Shin, Hong, Hea-Nam, Choi, Young-Il, Yoon, Sam-Youl, Won, You-Jin, Song, Gi-Won, Kim, Nayoung, Tak, Eunyoung, Ryoo, Baek-Yeol
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - pathology
Cell Movement - drug effects
Cell Proliferation - drug effects
Drug Synergism
Hep G2 Cells
Hepatocyte Growth Factor - administration & dosage
Humans
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
Niacinamide - administration & dosage
Niacinamide - analogs & derivatives
Phenylurea Compounds - administration & dosage
Vitamin K - administration & dosage
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Summary:Vitamin K plays a role in controlling cell growth. Anti-angiogenic effects of sorafenib lead to impairment of vitamin K uptake and induction of des-γ-carboxyprothrombin release by hepatocellular carcinoma (HCC) cells. We examined sorafenib and vitamin K individually and in combination regarding their ability to suppress migration and metastatic potential of HCC cells. HepG2 cells (HCC cell line) were treated with hepatocyte growth factor (HGF). E-Cadherin expression, phospho-MET (p-MET), and phospho-extracellular signal-regulated kinase (p-ERK) levels and cell migration were evaluated. HGF-stimulated HepG2 cells, which were treated with a combination of sorafenib and vitamin K, showed significantly increased expression of E-cadherin and impairment of migration ability compared to when treated with either agent alone. This combination therapy also induced marked inhibition of epithelial-mesenchymal transition phenotype; inhibition of HGF-stimulated cell proliferation, invasion and migration; and inhibition of HGF/c-MET signaling pathway. Levels of p-MET and p-ERK were also significantly reduced by this combination. Our experimental study demonstrated that sorafenib and vitamin K can function synergistically to inhibit the migration and proliferation of HCC cells. Combination therapy with sorafenib and vitamin K appears to be worthy of clinical trial with expectation of synergistic therapeutic effects.
ISSN:1791-7530