The antitumor effects of metformin are potentially mediated through LPA receptor inhibition
- PMID: 40073948
- DOI: 10.1016/j.diabres.2025.112094
The antitumor effects of metformin are potentially mediated through LPA receptor inhibition
Abstract
Aims: Although metformin has antitumor effects, the detailed mechanism of action, particularly with respect to the cellular responses mediated through G protein-coupled receptors (GPCRs), remains unclear.
Methods and results: Here, we assayed a panel of 200 GPCRs in cells treated with metformin and reported that signaling through several receptors, including lysophosphatidic acid (LPA) receptors, was suppressed. Metformin significantly attenuated LPA-induced intracellular Ca2+ mobilization in LPA receptor 1 (LPAR1)-, 2 (LPAR2)-, and 3 (LPAR3)-transfected rat hepatoma RH7777 cells. LPA treatment increased LPAR3-transfected RH7777 cell adhesion and migration. This response to LPA was attenuated by treatment with the Gq/11 inhibitor YM-254890 and metformin. In contrast, these inhibitors had minimal effects on the cell migration induced by epidermal growth factor.
Conclusions: These results indicate that the inhibition of LPA receptor signaling by metformin, especially the consequent suppression of LPAR3-mediated cell migration, may contribute to the antitumor effects of metformin.
Keywords: Antitumor effect; Cell migration; G protein-coupled receptor; Lysophosphatidic acid; Metformin; intracellular Ca(2+) mobilization.
Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.