Prevention of Rat Hepatocarcinogenesis by Acyclic Retinoid Is Accompanied by Reduction in Emergence of Both TGF-α-Expressing Oval-Like Cells and Activated Hepatic Stellate Cells

Authors:
  • MKMasataka Kagawa
    Masataka Kagawa
  • MOMasataka Okuno
    Masataka Okuno
  • NINaoto Ishibashi
    Naoto Ishibashi
  • MHManabu Hashimoto
    Manabu Hashimoto
  • MYMegumi Yamamoto
    Megumi Yamamoto
  • RSRikako Suzuki
    Rikako Suzuki
  • HKHiroyuki Kohno
    Hiroyuki Kohno
  • RMRie Matsushima-Nishiwaki
    Rie Matsushima-Nishiwaki
  • YTYukihiko Takano
    Yukihiko Takano
  • HTHisashi Tsurumi
    Hisashi Tsurumi
Publisher website
Google Scholar
Abstract
We investigated the preventive effects of a synthetic acyclic retinoid, NIK-333, on the early and late events of hepatocarcinogenesis in male F344 rats treated with 3'-methyl-4-dimethylaminoazobenzene (3'-MeDAB). NIK-333 was administered once a day on consecutive days at a dose of 10, 40, or 80 mg/kg body weight along with the supplementation with 3'-MeDAB-containing diet for 16 wk. Animals from each group were sacrificed at 4 and 16 wk after the commencement of the experiment to determine the effect of NIK-333 on the early and late stages of carcinogenesis, respectively. NIK-333 suppressed the emergence of both oval-like cells expressing transforming growth factor (TGF)-α, putative progenitors of hepatocellular carcinoma (HCC), and activated hepatic stellate cells, major matrix-producing cells of the liver, in the early stage and inhibited the incidence of HCC in the late phase. These results suggest that NIK-333 is a promising drug for the chemoprevention of HCC by uniquely suppressing the ear...

This publication has 31 references indexed in Scilit: