Infantile hemangioma (IH) is one of the most common benign vascular tumors of infancy. Propranolol has been recently introduced for the treatment of IH. However, the mechanism of protective effect has not been fully understood. In this study, hemangioma-derived endothelial cells (HemECs) were isolated and treated with propranolol. The cell viability was measured by MTT assay, and the cell cycle arrest was detected using flow cytometry. Cell invasion was determined using transwell assay. The expressions of matrix metalloproteinase (MMP)-2, MMP-9, Delta-like 4 (DLL4), Notch1, Akt, p-Akt, and vascular endothelial growth factor (VEGF) were detected using western blot. HemECs were incubated with recombinant human DLL4 (rhDLL4) to investigate the role of DLL4/Notch1 in the effect of propranolol. The results showed that propranolol inhibited cell viability of HemECs in a time-dependent manner. Propranolol suppressed cell proliferation of HemECs by arresting cell progression at G0/G1 phase. Propranolol inhibited the invasion ability of HemECs and reduced the expression levels of MMP-2 and MMP-9 in HemECs. Besides, propranolol treatment blocked the DLL4/Notch1 and Akt signaling and inhibited VEGF expression in HemECs. Treatment with rhDLL4 activated the Akt signaling and attenuated the effect of propranolol on HemECs. Our data indicated that propranolol inhibited the cell proliferation and invasion of HemECs. The effect was possibly involved in the DLL4/Notch1/Akt signaling pathway.

婴儿血管瘤（IH）是婴儿中最常见的良性血管肿瘤之一。最近已将普萘洛尔用于IH的治疗。但是，保护作用的机理尚未完全了解。在这项研究中，血管瘤来源的内皮细胞（HemECs）被分离并用心得安治疗。通过MTT测定法测量细胞活力，并使用流式细胞术检测细胞周期停滞。使用transwell测定法确定细胞侵袭。用western blot检测基质金属蛋白酶（MMP）-2，MMP-9，δ样4（DLL4），Notch1，Akt，p-Akt和血管内皮生长因子（VEGF）的表达。将HemEC与重组人DLL4（rhDLL4）孵育，以研究DLL4 / Notch1在心得安中的作用。结果表明，普萘洛尔以时间依赖性方式抑制HemECs的细胞活力。普萘洛尔通过在G0 / G1期阻止细胞进程来抑制HemECs的细胞增殖。普萘洛尔抑制HemECs的侵袭能力并降低HemECs中MMP-2和MMP-9的表达水平。此外，普萘洛尔治疗可阻断HemECs中的DLL4 / Notch1和Akt信号传导并抑制VEGF表达。rhDLL4处理可激活Akt信号转导，并减弱心得安对HemEC的作用。我们的数据表明，普萘洛尔抑制HemECs的细胞增殖和侵袭。该作用可能与DLL4 / Notch1 / Akt信号通路有关。普萘洛尔抑制HemECs的侵袭能力并降低HemECs中MMP-2和MMP-9的表达水平。此外，普萘洛尔治疗可阻断HemECs中的DLL4 / Notch1和Akt信号传导并抑制VEGF表达。rhDLL4处理可激活Akt信号转导，并减弱心得安对HemEC的作用。我们的数据表明，普萘洛尔抑制HemECs的细胞增殖和侵袭。该作用可能与DLL4 / Notch1 / Akt信号通路有关。普萘洛尔抑制HemECs的侵袭能力并降低HemECs中MMP-2和MMP-9的表达水平。此外，普萘洛尔治疗可阻断HemECs中的DLL4 / Notch1和Akt信号传导并抑制VEGF表达。rhDLL4处理可激活Akt信号转导，并减弱心得安对HemEC的作用。我们的数据表明，普萘洛尔抑制HemECs的细胞增殖和侵袭。该作用可能与DLL4 / Notch1 / Akt信号通路有关。我们的数据表明，普萘洛尔抑制HemECs的细胞增殖和侵袭。该作用可能与DLL4 / Notch1 / Akt信号通路有关。我们的数据表明，普萘洛尔抑制HemECs的细胞增殖和侵袭。该作用可能与DLL4 / Notch1 / Akt信号通路有关。