Metformin suppresses gastric cancer progression by disrupting the STAT1-PRMT1 axis.
Biochem Pharmacol
; 226: 116367, 2024 08.
Article
in En
| MEDLINE
| ID: mdl-38876258
ABSTRACT
Gastric cancer (GC) is a common form of cancer and the leading cause of cancer-related deaths worldwide. Chemotherapy is the primary treatment for patients with unresectable or partially resectable GC. However, its adverse effects and chemoresistance greatly restrict its applicability and efficacy. Although HER2-targeted therapy and immunotherapy have been successfully used for GC treatment, their beneficial population is limited. To expand the range of cancer treatments, drug repurposing has emerged as a promising strategy. In this study, we evaluated the potential of Metformin, an oral anti-hyperglycemic agent, to suppress GC progression both in vivo and in vitro. Functional investigations showed that Metformin significantly inhibits GC proliferation and migration. Furthermore, we discovered that Metformin bound and disrupted STAT1 phosphorylation, inhibiting PRMT1 expression and consequently GC progression. In conclusion, our study not only provides further evidence for the anti-GC role of Metformin but also identifies the direct target mediating the tumor-inhibitory effects of Metformin in GC.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein-Arginine N-Methyltransferases
/
Repressor Proteins
/
Stomach Neoplasms
/
STAT1 Transcription Factor
/
Metformin
/
Mice, Nude
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Biochem Pharmacol
/
Biochem. pharmacol
/
Biochemical pharmacology
Year:
2024
Type:
Article