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

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-γ (PPARγ) 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 PPARγ agonist pioglitazone on tumor metastasis and liver injury following IRI in a mouse model of colon cancer. Pioglitazone (30 mg/kg weight) was administered orally 1.5 h before and 2 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 × 106) were injected into the spleen. Fifteen minutes after injection, the hepatoduodenal ligament was clamped with a vessel clip, and released 5 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.

• Authors: Yoshihiko Tashiro, Hiroto Nishino, Takashi Higuchi, Norihiko Sugisawa, Yasunari Fukuda, Jun Yamamoto, Sachiko Inubushi, Takeshi Aoki, Masahiko Murakami, Shree Ram Singh, Michael Bouvet, Robert M Hoffman
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 18565 (10 29 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 33122687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytokines
• PPAR gamma
• Pioglitazone

Topics

• Animals
• Colonic Neoplasms (drug therapy, metabolism, pathology)
• Cytokines (metabolism)
• Disease Models, Animal
• Disease Progression
• Inflammation (drug therapy, metabolism, pathology)
• Liver (drug effects, metabolism, pathology)
• Liver Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis (drug therapy, pathology)
• PPAR gamma (agonists)
• Pioglitazone (pharmacology)
• Reperfusion Injury (metabolism, pathology)
• Spleen (drug effects, metabolism, pathology)