RT Journal Article SR Electronic T1 Synergistic Effect of Sorafenib and Vitamin K on Suppression of Hepatocellular Carcinoma Cell Migration and Metastasis JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 1985 OP 1995 VO 35 IS 4 A1 HA, TAE-YONG A1 HWANG, SHIN A1 HONG, HEA-NAM A1 CHOI, YOUNG-IL A1 YOON, SAM-YOUL A1 WON, YOU-JIN A1 SONG, GI-WON A1 KIM, NAYOUNG A1 TAK, EUNYOUNG A1 RYOO, BAEK-YEOL YR 2015 UL http://ar.iiarjournals.org/content/35/4/1985.abstract AB 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.