biostudies-literatureDing XJNatural Science Foundation of Tianjin MunicipalityNational Natural Science Foundation of ChinaTianjin Key Medical Discipline (Specialty) Construction Projecte70028https://www.ebi.ac.uk/biostudies/studies/S-EPMC11868026biostudies-literatureUnknown16(5)<h4>Background</h4>Improving the "cold" tumor immune microenvironment (TIME) of small-cell lung cancer (SCLC) represents a promising therapeutic approach. The metabolite lactate plays a crucial role in shaping the immune-cold tumor microenvironment (TME) and facilitating tumor progression. Phosphoglycerate kinase 1 (PGK1) is a key enzyme involved in tumor lactate metabolism. This study demonstrates that ACT001 improves the TIME of SCLC through inhibiting lactate production by targeting PGK1.<h4>Methods</h4>The cytotoxic effects of ACT001 on SCLC cell lines NCI-H1688 and NCI-H446 were evaluated using MTT assay, clone formation, EdU incorporation, wound healing, and invasion assays. To elucidate the mechanism of action of ACT001, proteomic techniques, pull-down assays, LC-MS/MS, surface plasThoracic cancerACT001 Suppresses the Malignant Progression of Small-Cell Lung Cancer by Inhibiting Lactate Production and Promoting Anti-Tumor Immunity.PMC118680268217263521JCYBJC0100082273794TJYXZDXK-010A8220362882272686Wang WJLu YXDing XJQin TTHuang DZMei TChen YXi XNWang JYfalseACT001 Suppresses the Malignant Progression of Small-Cell Lung Cancer by Inhibiting Lactate Production and Promoting Anti-Tumor Immunity.<h4>Background</h4>Improving the "cold" tumor immune microenvironment (TIME) of small-cell lung cancer (SCLC) represents a promising therapeutic approach. The metabolite lactate plays a crucial role in shaping the immune-cold tumor microenvironment (TME) and facilitating tumor progression. Phosphoglycerate kinase 1 (PGK1) is a key enzyme involved in tumor lactate metabolism. This study demonstrates that ACT001 improves the TIME of SCLC through inhibiting lactate production by targeting PGK1.<h4>Methods</h4>The cytotoxic effects of ACT001 on SCLC cell lines NCI-H1688 and NCI-H446 were evaluated using MTT assay, clone formation, EdU incorporation, wound healing, and invasion assays. To elucidate the mechanism of action of ACT001, proteomic techniques, pull-down assays, LC-MS/MS, surface plas2025-01-01T00:00:00Z2025 Mar2025-04-22T20:07:57.092Z2025-04-06T03:05:01.695ZS-EPMC118680264001697110.1111/1759-7714.70028