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

研究成果: Article

26 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)1175-1181
ページ数7
ジャーナルJapanese Journal of Cancer Research
93
発行部数10
DOI
出版物ステータスPublished - 2002 10 1
外部発表Yes

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Indomethacin
Aspirin
Hepatocellular Carcinoma
Neoplasm Metastasis
Lung
Diethylnitrosamine
Vascular Cell Adhesion Molecule-1
Inbred F344 Rats
Vascular Endothelium
Intercellular Adhesion Molecule-1
Cadherins
Drinking Water
Carcinogens
Endothelium
Neoplasms
Anti-Inflammatory Agents
Body Weight
Cell Proliferation
Diet
Control Groups

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

これを引用

Suppression of lung metastasis by aspirin but not indomethacin in an in vivo model of chemically induced hepatocellular carcinoma. / Toriyama-Baba, Hiroyasu; Ligo, Masaaki; Asamoto, Makoto; Iwahori, Yoshio; Park, Cheol Beom; Han, Beom Seok; Takasuka, Nobuo; Kakizoe, Tadao; Ishikawa, Chikako; Yazawa, Kazunaga; Araki, Eiji; Tsuda, Hiroyuki.

:: Japanese Journal of Cancer Research, 巻 93, 番号 10, 01.10.2002, p. 1175-1181.

研究成果: Article

Toriyama-Baba, H, Ligo, M, Asamoto, M, Iwahori, Y, Park, CB, Han, BS, 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, 巻. 93, 番号 10, pp. 1175-1181. https://doi.org/10.1111/j.1349-7006.2001.tb02137.x
Toriyama-Baba, Hiroyasu ; Ligo, Masaaki ; Asamoto, Makoto ; Iwahori, Yoshio ; Park, Cheol Beom ; Han, Beom Seok ; Takasuka, Nobuo ; Kakizoe, Tadao ; Ishikawa, Chikako ; Yazawa, Kazunaga ; Araki, Eiji ; Tsuda, Hiroyuki. / Suppression of lung metastasis by aspirin but not indomethacin in an in vivo model of chemically induced hepatocellular carcinoma. :: Japanese Journal of Cancer Research. 2002 ; 巻 93, 番号 10. pp. 1175-1181.
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title = "Suppression of lung metastasis by aspirin but not indomethacin in an in vivo model of chemically induced hepatocellular carcinoma",
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.",
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author = "Hiroyasu Toriyama-Baba and Masaaki Ligo and Makoto Asamoto and Yoshio Iwahori and Park, {Cheol Beom} and Han, {Beom Seok} and Nobuo Takasuka and Tadao Kakizoe and Chikako Ishikawa and Kazunaga Yazawa and Eiji Araki and Hiroyuki Tsuda",
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T1 - Suppression of lung metastasis by aspirin but not indomethacin in an in vivo model of chemically induced hepatocellular carcinoma

AU - Toriyama-Baba, Hiroyasu

AU - Ligo, Masaaki

AU - Asamoto, Makoto

AU - Iwahori, Yoshio

AU - Park, Cheol Beom

AU - Han, Beom Seok

AU - Takasuka, Nobuo

AU - Kakizoe, Tadao

AU - Ishikawa, Chikako

AU - Yazawa, Kazunaga

AU - Araki, Eiji

AU - Tsuda, Hiroyuki

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N2 - 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.

AB - 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.

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