SB218078 inhibits angiogenesis and epithelial-mesenchymal transition in breast cancer

• DOI: 10.3389/fphar.2025.1552707
• Publication Date: 2025-03-14T07:09:30Z
• Authors: Qianxue Wu; Jiawei Xu; Xin Tang; Jin Yu; Benhua Li; Jun Yang; Xiang Zhang

Small-molecule inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2) face clinical limitations due to adverse effects. This study aimed evaluate the novel compound SB218078 as a dual-targeting agent against both tumor angiogenesis and epithelial-mesenchymal transition (EMT) in breast cancer, while exploring its mechanisms action. The anti-angiogenic effects were investigated using vitro models cell migration, invasion, tube formation, alongside vivo zebrafish developmental assays. Breast cancer progression was assessed through cellular proliferation, invasion tests, mouse xenograft models. Mechanistic studies focused on Chk1/ZEB1 signaling axis, validated genetic interventions. effectively suppressed by inhibiting functions disrupting networks zebrafish. It also impeded aggressiveness vivo. Mechanistically, selectively targeted ZEB1-an EMT transcription factor-via Chk1 inhibition, with ZEB1 knockdown mimicking effects, overexpression reversed this activity. emerges promising dual-action therapeutic candidate for simultaneously blocking Chk1-ZEB1 axis. Its specificity ZEB1, distinct from other regulators, offers strategy overcome traditional VEGFR2 inhibitors, warranting further preclinical development.