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Ischemia reperfusion-induced metastasis is resistant to PPAR? agonist pioglitazone in a murine model of colon cancer

  1. Author:
    Tashiro, Yoshihiko
    Nishino, Hiroto
    Higuchi, Takashi
    Sugisawa, Norihiko
    Fukuda, Yasunari
    Yamamoto, Jun
    Inubushi, Sachiko
    Aoki, Takeshi
    Murakami, Masahiko
    Singh,Shree Ram
    Bouvet, Michael
    Hoffman, Robert M

  2. Author Address

    AntiCancer Inc, 7917 Ostrow St, San Diego, CA, 92111, USA., Department of Surgery, University of California, San Diego, CA, USA., Department of General and Gastroenterological Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan., Department of General and Gastroenterological Surgery, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8666, Japan. takejp@med.showa-u.ac.jp., Basic Research Laboratory, National Cancer Institute, Frederick, MD, 21702, USA. singhshr@mail.nih.gov., AntiCancer Inc, 7917 Ostrow St, San Diego, CA, 92111, USA. all@anticancer.com., Department of Surgery, University of California, San Diego, CA, USA. all@anticancer.com.,
    1. Year: 2020
    2. Date: Oct 29
    3. Epub Date: 2020 10 29
  2. Journal: Scientific reports
    1. 10
    2. 1
    3. Pages: 18565
  4. Type of Article: Article
  5. Article Number: 18565
  6. ISSN: 2045-2322
  1. Abstract:

    Ischemia reperfusion injury (IRI) during liver-metastasis resection for treatment of colon cancer may increase the risk of further metastasis. Peroxisome proliferator-activated receptor-? (PPAR?) activation has been observed to exert a protective effect against IRI and IRI-induced metastasis of hepatocellular carcinoma. The present study aimed to investigate the effect of the PPAR? agonist pioglitazone on tumor metastasis and liver injury following IRI in a mouse model of colon cancer. Pioglitazone (30 160;mg/kg weight) was administered orally 1.5 160;h before and 2 160;h after the initiation of ischemia and was orally administrated daily to mice from day 0-21. SL4-cancer cells expressing red fluorescent protein (SL4-RFP) (1? 215;?106) were injected into the spleen. Fifteen minutes after injection, the hepatoduodenal ligament was clamped with a vessel clip, and released 5 160;min later. Liver, blood and tumor samples were taken from mice in order to determine if inflammation was induced by IRI. The effect of pioglitazone on liver metastasis was assessed. Furthermore, the effect of pioglitazone to control the inflammatory response during IRI progression was examined. Liver metastasis along with MMP-9 activation and the production of inflammatory cytokines were resistant to pioglitazone. Our results indicate that liver metastasis and associated inflammation in mice were resistant to pioglitazone.

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External Sources

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  2. DOI: 10.1038/s41598-020-75210-6
  3. PMID: 33122687
  4. PMCID: PMC7596558
  5. View record in Web of Science®
  6. WOS: 000587689500028
  7. PII : 10.1038/s41598-020-75210-6

Library Notes

  1. Fiscal Year: FY2020-2021
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