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- Title
GPR43 Suppresses Intestinal Tumor Growth by Modification of the Mammalian Target of Rapamycin Complex 1 Activity in ApcMin/+ Mice.
- Authors
Kong, Lingling; Hoshi, Namiko; Sui, Yunlong; Yamada, Yasutaka; Yoshida, Ryutaro; Ooi, Makoto; Tian, Zibin; Kimura, Ikuo; Kodama, Yuzo
- Abstract
<bold>Objective: </bold>G protein-coupled receptor 43 (GPR43), a receptor for short-chain fatty acids, plays a role in suppressing tumor growth; however, the detailed underlying mechanism needs to be comprehensively elucidated. In this study, we investigated the role of GPR43 in inhibiting tumor growth using ApcMin/+, a murine model of intestinal tumors.<bold>Materials and Methods: </bold>Using GPR43-/- ApcMin/+ and GPR43+/- ApcMin/+ mice, the number of tumors was analyzed at the end of the experimental period. Immunohistochemistry, quantitative polymerase chain reaction, and Western blotting were performed to analyze cellular proliferation and proliferation-associated signal pathways.<bold>Results: </bold>Our results revealed that GPR43 deficiency resulted in increased tumor numbers in ApcMin/+ mice. Ki67 was highly expressed in GPR43-/- mice (p > 0.05). Increased expression levels of proinflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, and amino acid transporters were not observed in GPR43-deficient mice compared to GPR43-sufficient mice. Furthermore, GPR43-deficient tumor tissues showed enhanced mammalian target of rapamycin-mediated phosphorylated ribosomal protein S6 kinase beta-1 (p > 0.05) and phosphorylated eukaryotic translation initiation factor 4E-binding protein 1 (p > 0.05), but not Akt (protein kinase B) phosphorylation (p = 0.7088).<bold>Conclusion: </bold>Collectively, GPR43 affords protection against tumor growth at least partly through inhibition of the mammalian target of rapamycin complex 1 pathway.
- Subjects
INTESTINAL tumors; TUMOR growth; MTOR inhibitors; RAPAMYCIN; PROTEIN kinase B; G protein coupled receptors; SHORT-chain fatty acids; RIBOSOMAL proteins; MAMMAL metabolism; COLON (Anatomy); MENTAL health surveys; RESEARCH funding; INTESTINAL mucosa; MICE; ANIMALS
- Publication
Medical Principles & Practice, 2022, Vol 31, Issue 1, p39
- ISSN
1011-7571
- Publication type
journal article
- DOI
10.1159/000518621