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 TAE-YONG HA
A1 SHIN HWANG
A1 HEA-NAM HONG
A1 YOUNG-IL CHOI
A1 SAM-YOUL YOON
A1 YOU-JIN WON
A1 GI-WON SONG
A1 NAYOUNG KIM
A1 EUNYOUNG TAK
A1 BAEK-YEOL RYOO
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.