Cycloartenol attenuates cell motion and angiogenesis by regulating VEGFA/VEGFR2 signaling pathway in gastric cancer

Xiaotansanjiefang, a traditional Chinese medicine formula containing pinellia rhizomes, is investigated for anti-gastric cancer (GC) activity. Cycloartenol, a triterpenoid saponin from pinellia, exhibits emerging anti-tumor properties. This study evaluates its effects on GC cell migration, invasion, and angiogenesis. Cytotoxicity of cycloartenol (0-160 μM) was assessed in GC cells (AGS and MKN-45) and immortalized normal gastric epithelial cells (GES-1) via MTT assays. Colony formation, wound healing, and Transwell assays were conducted to assess proliferation, migration, and invasion. Angiogenesis was evaluated by HUVEC tube formation using conditioned media harvested from cycloartenol-treated GC cells. VEGFA and VEGFR2 protein levels were measured by Western blotting. Cycloartenol showed dose-dependent cytotoxicity in GC cells with minimal toxicity toward GES-1 cells, indicating selectivity. It suppressed colony formation, delayed wound closure, reduced invading cells, and inhibited HUVEC tube formation. Consistently, cycloartenol downregulated VEGFA and VEGFR2 expression in GC cells and HUVECs. In conclusion, cycloartenol selectively suppresses GC cell growth, migration, invasion, and angiogenesis through inactivation of the VEGFA/VEGFR2 pathway.