Metformin promotes anti-tumor immunity in STK11 mutant NSCLC through AXIN1-dependent upregulation of multiple nucleotide metabolites
ZHIGUO WANG1,2,#, KUNLIN LI2,#, CONGHUA LU2, MINGXIA FENG2, CAIYU LIN2, GUOFANG YIN1, DAN LUO1, WENYI LIU3, KAIYU JIN4, YUANYAO DOU2, DI WU2, JIE ZHENG2, KEJUN ZHANG5, LI LI2,*, XIANMING FAN1,*
Oncology Research, Vol.32, No.10, pp. 1637-1648, 2024, DOI:10.32604/or.2024.052664
- 18 September 2024
(This article belongs to the Special Issue: New Era in Cancer Treatment: Advances in Targeted and Pharmacological Therapies with the Subtle Integration of Multi-Omics)
Abstract Background: Metformin has pleiotropic effects beyond glucose reduction, including tumor inhibition and immune regulation. It enhanced the anti-tumor effects of programmed cell death protein 1 (PD-1) inhibitors in serine/threonine kinase 11 (STK11) mutant non-small cell lung cancer (NSCLC) through an axis inhibition protein 1 (AXIN1)-dependent manner. However, the alterations of tumor metabolism and metabolites upon metformin administration remain unclear. Methods: We performed untargeted metabolomics using liquid chromatography (LC)-mass spectrometry (MS)/MS system and conducted cell experiments to verify the results of bioinformatics analysis. Results: According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, most… More >
Graphic Abstract