In vivo experiments demonstrated that COE significantly decreases the immunohistochemical staining intensity of Notch1 and Hes1 in tumor tissues, downregulates the expression of EphA2, MMP2/9, VE-cadherin, Twist1, while upregulating E-cadherin expression, and reduces the number of CD31-/PAS+ and CD34-/PAS+ double-positive VM structures, further validating its inhibitory effect on VM formation in HCC (Jue et al., 2017b; Chu et al., 2021). Here, HES1 is linked to neoplasm.