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.

Details

Title
Ischemia reperfusion-induced metastasis is resistant to PPARγ agonist pioglitazone in a murine model of colon cancer
Author
Tashiro, Yoshihiko 1 ; Nishino, Hiroto 2 ; Higuchi, Takashi 2 ; Sugisawa, Norihiko 2 ; Fukuda, Yasunari 2 ; Yamamoto, Jun 2 ; Inubushi, Sachiko 2 ; Aoki, Takeshi 3 ; Murakami, Masahiko 3 ; Singh, Shree Ram 4 ; Bouvet, Michael 5 ; Hoffman, Robert M. 2 

 AntiCancer Inc, San Diego, USA (GRID:grid.417448.a) (ISNI:0000 0004 0461 1271); University of California, Department of Surgery, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242); Showa University School of Medicine, Department of General and Gastroenterological Surgery, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
 AntiCancer Inc, San Diego, USA (GRID:grid.417448.a) (ISNI:0000 0004 0461 1271); University of California, Department of Surgery, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
 Showa University School of Medicine, Department of General and Gastroenterological Surgery, Tokyo, Japan (GRID:grid.410714.7) (ISNI:0000 0000 8864 3422) 
 National Cancer Institute, Basic Research Laboratory, Frederick, USA (GRID:grid.48336.3a) (ISNI:0000 0004 1936 8075) 
 University of California, Department of Surgery, San Diego, USA (GRID:grid.266100.3) (ISNI:0000 0001 2107 4242) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2471528021
Copyright
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.