Dauriporphine Inhibits the Proliferation, Migration, Angiogenesis, and Glycolysis in Lung Cancer Cells by Repressing <scp>PGK1</scp> Expression via <scp>CEBPA</scp>

Many anti-cancer agents with therapeutic potential have been discovered in traditional Chinese medicine. Dauriporphine is an alkaloid extracted from Menispermum dauricum DC., demonstrating anti-cancer properties. However, the precise role of dauriporphine in the treatment of lung cancer and its underlying biological mechanism remains unclear. Dauriporphine addition resulted in reduced proliferation, migration, angiogenesis, and glycolysis in A549 and H1299 cells. Phosphoglycerate kinase 1 (PGK1) was identified as the candidate gene involved in glycolysis and dauriporphine after prediction using public datasets. Dauriporphine administration decreased PGK1 expression, whereas PGK1 overexpression markedly abolished the suppressive effects of dauriporphine. The CCAAT/enhancer binding protein A (CEBPA) was predicted to be the transcription factor of PGK1 using the online QIAGEN. The binding between CEBPA and PGK1 promoter was predicted and verified using Jaspar algorithm and Human TFDB, as well as chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, and cellular thermal shift assay (CETSA). CEBPA silencing could repress tumor cell malignant behaviors, which could be partially restored by PGK1 overexpression. Moreover, the upregulation of CEBPA diminished the anti-tumor efficacy of dauriporphine. Furthermore, dauriporphine treatment suppressed tumor growth by regulating the CEBPA/PGK1 pathway in nude mice. Overall, the study demonstrated that dauriporphine inhibited proliferation, migration, angiogenesis, and glycolysis in lung cancer cells via the CEBPA/PGK1 pathway, providing a potentially effective therapeutic strategy for lung cancer.