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GPR43 Suppresses Intestinal Tumor Growth by Modification of the Mammalian Target of Rapamycin Complex 1 Activity in ApcMin/+ Mice.


ABSTRACT:

Objective

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.

Materials and methods

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.

Results

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).

Conclusion

Collectively, GPR43 affords protection against tumor growth at least partly through inhibition of the mammalian target of rapamycin complex 1 pathway.

SUBMITTER: Kong L 

PROVIDER: S-EPMC8995667 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

GPR43 Suppresses Intestinal Tumor Growth by Modification of the Mammalian Target of Rapamycin Complex 1 Activity in ApcMin/+ Mice.

Kong Lingling L   Hoshi Namiko N   Sui Yunlong Y   Yamada Yasutaka Y   Yoshida Ryutaro R   Ooi Makoto M   Tian Zibin Z   Kimura Ikuo I   Kodama Yuzo Y  

Medical principles and practice : international journal of the Kuwait University, Health Science Centre 20211001 1


<h4>Objective</h4>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.<h4>Materials and methods</h4>Using GPR43-/- ApcMin/+ and GPR43+/- ApcMin/+ mice, the number of tumors was analyzed at the end of the experimental per  ...[more]

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