| RRC ID |
89465
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| 著者 |
Noma T, Li Y, Wada Y, Morine Y, Ikemoto T, Saito Y, Shimada M, Goel A.
|
| タイトル |
GLP-1 receptor agonist targets an AMPKα1-HIF1α-PFKFB3 metabolic vulnerability and enhances Lenvatinib response in hepatocellular carcinoma.
|
| ジャーナル |
NPJ Precis Oncol
|
| Abstract |
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for diabetes and obesity, have recently attracted attention for potential anti-tumor effects, although their mechanisms remain unclear. Given their role in metabolic regulation, we hypothesized that GLP-1RAs may target cancer-specific metabolic vulnerabilities. Hepatocellular carcinoma (HCC) is characterized by metabolic reprogramming and enhanced glycolysis, which contribute to therapeutic resistance. Here, we investigated the anti-tumor effects of a GLP-1RA in HCC, focusing on its ability to modulate glycolytic pathways and enhance sensitivity to Lenvatinib. Lenvatinib-resistant HCC cells exhibited suppressed AMPKα1 and increased HIF-1α and PFKFB3 expression, promoting glycolytic adaptation. GLP-1RA treatment restored AMPKα1 activity while suppressing HIF-1α/PFKFB3 signaling, thereby reducing glycolytic activity and enhancing apoptosis. Combination treatment with GLP-1RA and Lenvatinib significantly inhibited tumor cell growth in resistant models. These findings suggest that the AMPKα1/HIF-1α/PFKFB3 axis represents a metabolic vulnerability in Lenvatinib-resistant HCC and support GLP-1RA-based combination strategies.
|
| 公開日 |
2026-6-29
|
| DOI |
10.1038/s41698-026-01584-x
|
| PII |
10.1038/s41698-026-01584-x
|
| PMID |
42373728
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-7(RCB1366) |
