Cover Image

Tumor Shrinkage in Response to Vitamin K2 in Hepatocellular Carcinoma with Multiple Lung Metastases: A Case Report

Hiromitsu Hayashi, Takaaki Higashi, Hideaki Takeyama, Keita Sakamoto, Hideyuki Kuroki, Hidetoshi Nitta, Daisuke Hashimoto, Akira Chikamoto, Toru Beppu, Hideo Baba


Introduction: Advanced or metastatic hepatocellular carcinoma (HCC) can be lethal because of the limited therapeutic approach such as sorafenib. Recently, Vitamin K2 (VK2) has been increasingly recognized to have anti-cancer effects for HCC in vitro and vivo. However, the direct anti-cancer effect of VK2 to HCC has not been established yet in human.

Presentation of Case: We presented here a 88-year-HCC patient displayed a tumor shrinkage in response to VK2 in multiple lung metastases, indicating the possibility of VK2 as an anti-cancer agent in human. Menatetrenone, a VK2 analogue, was introduced for multiple lung metastases as a palliative treatment, and thereafter multiple lung metastases, except one lung lesion, displayed tumor shrinkage and disappeared within five months after VK2 intake. The residual one lesion continued to grow up during the intake of VK2, suggesting that the residual tumor was insensitive to VK2 represented by tumor heterogeneity. Consequently, after a radiation therapy for the residual lesion, the elevated tumor markers of all were finally decreased into normal levels, and he is still alive for 18 months after VK2 intake without elevated tumor marker levels and toxic adverse effects.

Conclusion:VK2 may be a therapeutic option for advanced and metastatic HCCs without any toxic adverse.


hepatocellular carcinoma; vitamin K;menatetrenone

Full Text:



Rimassa L, Santoro A. Sorafenib therapy in advanced hepatocellular carcinoma: The sharp trial. Expert review of anticancer therapy. 2009, 9:739-745

Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J, Sun Y, Liang H, Liu J, Wang J, Tak WY, Pan H, Burock K, Zou J, Voliotis D, Guan Z. Efficacy and safety of sorafenib in patients in the asia-pacific region with advanced hepatocellular carcinoma: A phase iii randomised, double-blind, placebo-controlled trial. The lancet oncology. 2009, 10:25-34

Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J. Sorafenib in advanced hepatocellular carcinoma. The New England journal of medicine. 2008, 359:378-390

Otsuka M, Kato N, Shao RX, Hoshida Y, Ijichi H, Koike Y, Taniguchi H, Moriyama M, Shiratori Y, Kawabe T, Omata M. Vitamin k2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase a activation. Hepatology. 2004, 40:243-251

Matsumoto K, Okano J, Nagahara T, Murawaki Y. Apoptosis of liver cancer cells by vitamin k2 and enhancement by mek inhibition. International journal of oncology. 2006, 29:1501-1508

Ozaki I, Zhang H, Mizuta T, Ide Y, Eguchi Y, Yasutake T, Sakamaki T, Pestell RG, Yamamoto K. Menatetrenone, a vitamin k2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin d1 expression through inhibition of nuclear factor kappab activation. Clinical cancer research : an official journal of the American Association for Cancer Research. 2007, 13:2236-2245

Liu W, Nakamura H, Yamamoto T, Ikeda N, Saito M, Ohno M, Hara N, Imanishi H, Shimomura S, Yamamoto T, Sakai T, Nishiguchi S, Hada T. Vitamin k2 inhibits the proliferation of hepg2 cells by up-regulating the transcription of p21 gene. Hepatology research : the official journal of the Japan Society of Hepatology. 2007, 37:360-365

Zhang H, Ozaki I, Hamajima H, Iwane S, Takahashi H, Kawaguchi Y, Eguchi Y, Yamamoto K, Mizuta T. Vitamin k2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting nf-kappab activation. Oncology reports. 2011, 25:159-166

Wei G, Wang M, Hyslop T, Wang Z, Carr BI. Vitamin k enhancement of sorafenib-mediated hcc cell growth inhibition in vitro and in vivo. International journal of cancer. Journal international du cancer. 2010, 127:2949-2958

Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, Yamamoto K, Koike Y, Saito K, Koyanagi N, Kawabe T, Kawazoe S, Kobashi H, Kasugai H, Osaki Y, Araki Y, Izumi N, Oka H, Tsuji K, Toyota J, Seki T, Osawa T, Masaki N, Ichinose M, Seike M, Ishikawa A, Ueno Y, Tagawa K, Kuromatsu R, Sakisaka S, Ikeda H, Kuroda H, Kokuryu H, Yamashita T, Sakaida I, Katamoto T, Kikuchi K, Nomoto M, Omata M. Effect of vitamin k2 on the recurrence of hepatocellular carcinoma. Hepatology. 2011, 54:532-540

Riaz IB, Riaz H, Riaz T, Rahman S, Amir M, Badshah MB, Kazi AN. Role of vitamin k2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: A meta-analysis of randomized controlled trials. BMC gastroenterology. 2012, 12:170


  • There are currently no refbacks.

AJCC-REP (ISSN 2572-5742)Copyright © 2012-2021. All rights reserved. Published by Ivy Union Publishing, 3204 Valley Rush Dr, Apex, North Carolina 27502, United States