Suppression of lung metastasis by aspirin but not indomethacin in an in vivo model of chemically induced hepatocellular carcinoma

Hiroyasu Toriyama-Baba, Masaaki Ligo, Makoto Asamoto, Yoshio Iwahori, Cheol Beom Park, Beom Seok Han, Nobuo Takasuka, Tadao Kakizoe, Chikako Ishikawa, Kazunaga Yazawa, Eiji Araki, Hiroyuki Tsuda

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27 Citations (Scopus)

Abstract

To examine the effect of non-steroidal anti-inflammatory drugs on metastasis formation, aspirin (ASP, 0.5% in diet) and indomethacin (IM, 0.005% in drinking water) were applied to an in vivo highly metastatic rat hepatocellular carcinoma (HCC model in F344 male rats. Administration for 8 weeks after induction of highly metastatic HCC by sequential treatment with diethylnitrosamine and N-nitrosomorpholine did not cause any significant change in survival rate or body weight. Multiplicity of HCC in the liver increased during ASP or IM treatment without any significant histological alteration. Although absent in the rats killed at the end of the period of carcinogen exposure, lung metastasis at the end of the experiment was found in 100%, 89% and 100% of rats in the control, ASP and IM groups, respectively. Degree of metastasis was classified into three groups according to the number of metastatic nodules, i.e., slight (1-5 nodules), moderate (6-50) and severe (more than 51), which amounted to 0%, 43% and 57% in the control group. ASP significantly reduced the degree of metastasis, the incidences being 33%, 44%, and 11%, respectively, whereas IM was without significant influence. Both agents suppressed cell proliferation in HCCs, without any alteration of pan-cadherin expression. However, expression in HCC of mRNAs for intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, both of which are considered to play key roles in attachment of cancer cells to the endothelium, was significantly suppressed by ASP. Thus, the present study demonstrated that ASP, but not IM, has the potential to inhibit lung metastasis of rat HCC in vivo, possibly via reduced attachment of tumor cells to the vascular endothelium. Moreover, these data indicate this in vivo model for induction of rat highly metastatic HCC to be a useful tool for the assessment of the efficacy of therapeutic treatments to block metastasis formation.

Original languageEnglish
Pages (from-to)1175-1181
Number of pages7
JournalJapanese Journal of Cancer Research
Volume93
Issue number10
DOIs
Publication statusPublished - 2002 Oct 1
Externally publishedYes

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Keywords

  • Aspirin
  • In vivo lung metastasis model
  • Indomethacin
  • Lung metastasis
  • VCAM-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Toriyama-Baba, H., Ligo, M., Asamoto, M., Iwahori, Y., Park, C. B., Han, B. S., Takasuka, N., Kakizoe, T., Ishikawa, C., Yazawa, K., Araki, E., & Tsuda, H. (2002). Suppression of lung metastasis by aspirin but not indomethacin in an in vivo model of chemically induced hepatocellular carcinoma. Japanese Journal of Cancer Research, 93(10), 1175-1181. https://doi.org/10.1111/j.1349-7006.2001.tb02137.x