Baicalin inhibits bladder cancer progression by suppressing PD-L1-mediated M2 macrophage polarization via ALDH2.

This study aims to elucidate the anti-tumor mechanism of baicalin in bladder cancer (BCa), with a focus on the role of baicalin in tumor-associated macrophage polarization. BCa-related differentially expressed genes (DEGs) were detected using the GSE13507 dataset and intersected with predicted targets of baicalin to screen for core targets. Aldehyde dehydrogenase 2 (ALDH2) expression was assessed by RT-qPCR and Western blotting. An ALDH2-knockdown cell line was established for co-culture with bone marrow-derived macrophages (BMDMs) to evaluate macrophage polarization. Cellular behaviors were assessed respectively. An in vivo xenograft mouse model was used to validate the anti-tumor effects of baicalin. ALDH2 was downregulated in BCa. Baicalin directly bound to and upregulated ALDH2 expression. Elevated ALDH2 downregulated programmed death-ligand 1 (PD-L1) and promoted M1 macrophage polarization, thereby enhancing anti-tumor immune responses. Baicalin significantly inhibited the malignant phenotypes of BCa cells and reduced tumor growth in xenograft models. Notably, the anti-tumor effects of baicalin were partially reversed by ALDH2 knockdown or PD-L1 inhibition. Baicalin exerts potent anti-tumor effects in BCa by upregulating ALDH2, thereby suppressing PD-L1-mediated M2 macrophage polarization and remodeling the tumor immune microenvironment. This mechanism provides a novel therapeutic strategy for combating BCa progression.