Network pharmacology-based investigation and experimental validation of the mechanism of metformin in the treatment of acute myeloid leukemia

• Published in: European journal of medical research Vol. 29; no. 1; pp. 475 - 12
• Main Authors: Liu, Shaoyu, Xu, Mingming, Yang, Zhuofan, Li, Yangzi, Wu, Depei, Tang, Xiaowen
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.09.2024; BioMed Central; BMC
• Subjects: AML; Apoptosis; Apoptosis - drug effects; Cancer; Care and treatment; Cell Proliferation - drug effects; Diabetes therapy; Drug therapy; Gene Regulatory Networks - drug effects; Genes; Genomes; Genomics; HIF1A; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Network pharmacology; Network Pharmacology - methods; Pharmacology; Protein Interaction Maps - drug effects; Protein-protein interactions; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Type 2 diabetes; AML; Network pharmacology; Metformin; HIF1A; Apoptosis
• DOI: 10.1186/s40001-024-02022-z
• ISSN: 2047-783X; 0949-2321

Metformin, a widely used anti-diabetic agent, has shown significant anti-cancer properties as reported in in various cancers, including acute myeloid leukemia. However, the detailed mechanisms by which metformin influences acute myeloid leukemia remain unrevealed. Employing a synergistic approach of network pharmacology and experimental validation, this study systematically identifies and analyzes potential metformin targets and AML-related genes. These findings are then cross-referenced with biomedical databases to construct a target-gene network, providing insights into metformin's pharmacodynamics in AML treatment. Protein-Protein Interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses are utilized. Results show metformin's effectiveness in inhibiting AML cell proliferation and inducing apoptosis through the AKT/HIF1A/PDK1 signaling pathway. This research provides insights into metformin's clinical application in AML treatment.