Vitexin suppresses the proliferation, angiogenesis and stemness of endometrial cancer through the PI3K/AKT pathway

CONTEXT: Endometrial cancer is a common gynecologic malignancy. Vitexin is an active flavonoid compound with an antitumor function. OBJECTIVE: This study elucidated the role of vitexin in endometrial cancer development and clarified the potential mechanism. MATERIALS AND METHODS: The toxicity of vitexin (0–80 μM) treatment for 24 h on HEC-1B and Ishikawa cells was tested utilizing the CCK-8 assay. Endometrial cancer cells were divided into vitexin 0, 5, 10, and 20 μM groups. Cell proliferation, angiogenesis and stemness in vitro after treatment with vitexin (0, 5, 10, 20 μM) for 24 h were evaluated using the EdU staining assay, tube formation assay and sphere formation assay, respectively. Twelve BALB/c mice were grouped into control and vitexin (80 mg/kg) groups to monitor tumour growth for 30 days. RESULTS: Vitexin suppressed cell viability of HEC-1B (IC(50) = 9.89 μM) and Ishikawa (IC(50) = 12.35 μM) cells. The proliferation (55.3% and 80% for HEC-1B; 44.7% and 75% for Ishikawa), angiogenesis (54.3% and 78.4% for HEC-1B; 47.1% and 68.2% for Ishikawa) and stemness capacity (57.2% and 87.3% for HEC-1B; 53.4% and 78.4% for Ishikawa) of endometrial cancer cells were inhibited by 10 and 20 μM vitexin. Furthermore, the inhibitory effects of vitexin on endometrial cancer were reversed by PI3K/AKT agonist 740Y-P (20 μM). Moreover, the xenograft tumour experiment lasting for 30 days proved that vitexin (80 mg/kg) blocked tumour growth of endometrial cancer in vivo. DISCUSSION AND CONCLUSIONS: Vitexin has therapeutic potential on endometrial cancer, which supports further clinical trials.