Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation.
Although 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutic agents in various cancer including hepatocellular carcinoma (HCC), chemoresistance has precluded single use of 5-FU in clinical settings. Since menatetrenone, an analogue of vitamin K2 (VK2), inhibits growth of cancer cells including HCC cells in vitro and in vivo, we examined VK2 modulation of HCC cell response to 5-FU. VK2 pretreatment dose-dependently enhanced growth-inhibition by 5-FU through a G1 cell cycle arrest. VK2 inhibited 5-FU-induced NF-κB activation and cyclin D1 expression. Therefore, combination of VK2 and 5-FU might represent a new therapeutic strategy for patients with HCC.
Department of Surgery, The First Affiliated Hospital, China Medical University, Shenyang, P.R. China.
Hao
H
Zhang
Iwata
I
Ozaki
Hiroshi
H
Hamajima
Shinji
S
Iwane
Hirokazu
H
Takahashi
Yasunori
Y
Kawaguchi
Yuichiro
Y
Eguchi
Kyosuke
K
Yamamoto
Toshihiko
T
Mizuta
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D024202:Electrophoretic Mobility Shift Assay; D004789:Enzyme Activation / Q000187:drug effects; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024482:Vitamin K 2 / Q000031:analogs & derivatives / Q000494:pharmacology*
D000970:Antineoplastic Agents; D016328:NF-kappa B; D024482:Vitamin K 2; D005472:Fluorouracil