RRC ID 42189
著者 Otsuka M, Kato N, Shao RX, Hoshida Y, Ijichi H, Koike Y, Taniguchi H, Moriyama M, Shiratori Y, Kawabe T, Omata M.
タイトル Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation.
ジャーナル Hepatology
Abstract Hepatocellular carcinoma (HCC) is a common human malignancy. Its high mortality rate is mainly a result of high intrahepatic recurrence and portal venous invasion (PVI). We previously reported that the development of PVI is related to levels of des-gamma-carboxy prothrombin (DCP), a serum protein that increases at a notably higher rate in patients with HCC. Because DCP is produced by a vitamin K shortage, we examined the biological effects of extrinsic supplementation of vitamin K(2) in HCC cells in vitro and in vivo. Consequently, vitamin K(2) inhibits the growth and invasion of HCC cells through the activation of protein kinase A, which modulates the activities of several transcriptional factors and inhibits the small GTPase Rho, independent of suppression of DCP. In addition, administration of vitamin K(2) to nude mice inoculated with liver tumor cells reduced both tumor growth and body weight loss. In conclusion, similar to an acyclic retinoid--which was previously reported to prevent the recurrence of HCC--vitamin K(2), another lipid-soluble vitamin, may be a promising therapeutic means for the management of HCC.
巻・号 40(1)
ページ 243-51
公開日 2004-7-1
DOI 10.1002/hep.20260
PMID 15239108
MeSH Animals Carcinoma, Hepatocellular / enzymology* Carcinoma, Hepatocellular / pathology* Cell Division / drug effects Cell Line, Tumor Cyclic AMP-Dependent Protein Kinases / metabolism* Enzyme Activation Humans Liver Neoplasms / enzymology* Liver Neoplasms / metabolism Liver Neoplasms / pathology* Liver Neoplasms / physiopathology Mice Mice, Nude NIH 3T3 Cells Neoplasm Invasiveness Neoplasm Transplantation Signal Transduction / drug effects Vitamin K 2 / pharmacology* cdc25 Phosphatases / metabolism rhoA GTP-Binding Protein / antagonists & inhibitors
IF 14.679
引用数 99
WOS 分野 GASTROENTEROLOGY & HEPATOLOGY
リソース情報
ヒト・動物細胞 HepG2 NIH3T3