Apigenin inhibits recurrent bladder cancer progression by targeting VEGF-β

Abstract

Bladder cancer is a major global health concern with high incidence and mortality rates. Both muscle-invasive bladder cancer (MIBC) and recurrent non-muscle-invasive bladder cancer (NMIBC) present significant challenges in treatment. Apigenin, a naturally occurring flavonoid, has shown promise in inhibiting the growth of bladder cancer cells, however, its therapeutic mechanism remains unclear. Single-cell RNA sequencing (scRNA-seq) data analysis and drug target screening were performed. Differentially expressed genes (DEGs) and potential therapeutic targets of apigenin were identified. Molecular docking was utilized to evaluate the binding affinity between apigenin and VEGF-β. In vitro assays were conducted to evaluate the association of VEGF-β and apigenin. Drug target screening identified 51 common targets between apigenin and bladder cancer, with VEGF-β emerging as a dominant gene. Molecular docking confirmed a high binding affinity between apigenin and VEGF-β. VEGF-β was significantly upregulated in fibroblasts from recurrent bladder cancer, correlating with increased tumor malignancy. Enhanced cell communication in VEGF-β-positive fibroblasts contributed to tumor progression. In vitro experiments demonstrated that VEGF-β promotes tumor cell proliferation, migration, and invasion. Apigenin significantly inhibits bladder cancer progression by targeting VEGF-β. The upregulation of VEGF-β in fibroblasts from recurrent bladder cancer highlights its potential as a diagnostic marker and therapeutic target. This study underscores the promise of apigenin as a chemopreventive and therapeutic agent for recurrent bladder cancer.