The antitumor effects of metformin are potentially mediated through LPA receptor inhibition

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-03-10 DOI:10.1016/j.diabres.2025.112094

Koichi Sato , Hideaki Ogasawara , Yuichi Ikeda , Hidetoshi Kumagai , Ryota Inoue , Takahiro Tsuno , Koichi Matsunaga , Emi Ishida , Jun Shirakawa

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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 G_q/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.

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.