Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities

  • Authors:
    • Hitoshi Yoshiji
    • Shigeki Kuriyama
    • Ryuichi Noguchi
    • Junichi Yoshii
    • Yasuhide Ikenaka
    • Koji Yanase
    • Tadashi Namisaki
    • Mitsuteru Kitade
    • Masaharu Yamazaki
    • Takemi Akahane
    • Kiyoshi Asada
    • Tatsuhito Tsujimoto
    • Masahito Uemura
    • Hiroshi Fukui
  • View Affiliations

  • Published online on: January 1, 2006     https://doi.org/10.3892/or.15.1.155
  • Pages: 155-159
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Abstract

Recent studies have revealed that angiogenesis plays a pivotal role in carcinogenesis and tumor growth. We previously reported that the clinically used vitamin K2 (VK) and angiotensin-converting enzyme inhibitor (ACE-I) exerted potent anti-angiogenic activities. The aim of our current study was to examine the combination effect of VK and ACE-I on hepatocarcinogenesis induced by diethyl-nitrosamine, and orthotopic hepatocellular carcinoma (HCC) growth in rats. When used individually, both VK and ACE-I at clinically comparable low doses exerted significant inhibitory effects on tumor development in the liver. A combination treatment of VK and ACE-I showed a more potent suppressive effect against hepatocarcinogenesis. Neovascularization increased during hepatocarcinogenesis, and VK and ACE-I significantly attenuated angiogenesis in the tumor. In orthotopic HCC transplantation, VK and ACE-I also showed marked suppressive effects against HCC development similar to those against hepatocarcinogenesis. In both experiments, the suppressive effects of VK and ACE-I against angiogenesis were similar in magnitude to their inhibitory effects against hepatocarcinogenesis and orthotopic HCC development. In the orthotopic model, VK and ACE-I treatment resulted in a marked increase of apoptosis in the tumor, whereas tumor cell proliferation itself was not altered. Since both VK and ACE-I are widely used in clinical practice without serious side effects, this combination therapy may be an effective new therapeutic strategy against hepatocarcinogenesis and HCC growth in the future.

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January 2006
Volume 15 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yoshiji H, Kuriyama S, Noguchi R, Yoshii J, Ikenaka Y, Yanase K, Namisaki T, Kitade M, Yamazaki M, Akahane T, Akahane T, et al: Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncol Rep 15: 155-159, 2006.
APA
Yoshiji, H., Kuriyama, S., Noguchi, R., Yoshii, J., Ikenaka, Y., Yanase, K. ... Fukui, H. (2006). Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities. Oncology Reports, 15, 155-159. https://doi.org/10.3892/or.15.1.155
MLA
Yoshiji, H., Kuriyama, S., Noguchi, R., Yoshii, J., Ikenaka, Y., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Akahane, T., Asada, K., Tsujimoto, T., Uemura, M., Fukui, H."Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities". Oncology Reports 15.1 (2006): 155-159.
Chicago
Yoshiji, H., Kuriyama, S., Noguchi, R., Yoshii, J., Ikenaka, Y., Yanase, K., Namisaki, T., Kitade, M., Yamazaki, M., Akahane, T., Asada, K., Tsujimoto, T., Uemura, M., Fukui, H."Amelioration of carcinogenesis and tumor growth in the rat liver by combination of vitamin K2 and angiotensin-converting enzyme inhibitor via anti-angiogenic activities". Oncology Reports 15, no. 1 (2006): 155-159. https://doi.org/10.3892/or.15.1.155