STAT3 as a therapeutic target in the metformin-related treatment

• Published in: International immunopharmacology Vol. 116; p. 109770
• Main Authors: Zhang, Weiran, Li, Daisong, Li, Bing, Chu, Xianming, Kong, Bin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2023
• Subjects: AMP-Activated Protein Kinases - metabolism; Combination treatment; Humans; JAK; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Neoplasms - drug therapy; Review; Signal Transduction; STAT3; STAT3 Transcription Factor - metabolism; Combination treatment; Metformin; Review; JAK; STAT3
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2023.109770

[Display omitted] •Metformin has proved to be benifitial to various dseases.•STAT3 signaling plays an important role in mediating many pathological processes.•STAT3 signaling pathway is an important AMPK-independent pathway in metformin treatment. Signal transducers and activators of transcription 3 (STAT3) signaling plays an important role in mediating tumor progression, inflammation, cardiovascular disease, and other pathological processes.In recent years, STAT3 as a therapeutic target has received extensive attention. It is well known that metformin can play the role of hypoglycemia by activating AMP-activated protein kinase (AMPK) through inhibition of mitochondrial ATP production.However, AMPK is not required for metformin activity.Although the application of STAT3 as a therapeutic target of metformin is still in the initial research stage, the importance of STAT3 in the mechanism of metformin is gradually being recognizedand further studies are needed to demonstrate the important role of the STAT3 regulatory network in the regulation of diseases by metformin. Here, we reviewed in detail that metformin inhibits the progression of various diseases like tumors, autoimmune diseases and hormone-related diseases by regulating multiple signaling pathways such as JAK/STAT3 and mTOR/STAT3 signaling centered on STAT3. We also summarized recent advances of STAT3 inhibitors combined with metformin in the treatment of diseases.We emphasized that STAT3 signaling, as an AMPK-independent signaling pathway, may be an important target for metformin in clinical therapy.