Dong Jianyong, Cui Jun, Shi Xuanxuan, Wang Tao, Liu Shaohua
Department of Oral and Maxillofacial Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
Gao Xin Branch, Jinan Stomatological Hospital, Jinan, Shandong 250101, China.
Heliyon. 2023 Aug 22;9(9):e19244. doi: 10.1016/j.heliyon.2023.e19244. eCollection 2023 Sep.
Infantile hemangioma (IH) is among the most prevalent benign vascular tumours in infants. The pathogenesis of IH mainly involves abnormal proliferation of vascular endothelial cells and the formation of new vessels. Itraconazole was shown to be effective in treating IH; however, the mechanism underlying its action is still unclear. The purpose of this study was to examine the effects of itraconazole on the proliferation, apoptosis, and angiogenesis of hemangioma endothelial cells (HemECs); human umbilical vein endothelial cells served as the control group. The expression of genes involved in the hedgehog (HH) signaling pathway (SHH, PTCH1, SMO, and GLI1) was determined using real-time quantitative polymerase chain reaction. Western blotting was used to determine the expression of related proteins. In this study, itraconazole significantly dose- and time-dependently inhibited the viability of HemECs. Itraconazole suppressed the expression of PCNA, Ki67, and vascular endothelial growth factor (VEGF), demonstrating that this treatment inhibited cell proliferation and angiogenesis. Moreover, itraconazole induced apoptosis of HemECs by activating the expression of BAX and inhibiting the expression of BCL2. Itraconazole inhibited SHH, PTCH1, SMO, and GLI1 expression. Activation of the HH pathway by recombinant human sonic hedgehog (rhSHH) protein attenuated the effect of itraconazole on HemECs. In conclusion, itraconazole inhibits proliferation, induces apoptosis, and reduces angiogenesis of HemECs via the downregulation of the HH signaling pathway. Therefore, itraconazole may be an alternative choice for the treatment of IH.
婴儿血管瘤（IH）是婴儿中最常见的良性血管肿瘤之一。IH的发病机制主要涉及血管内皮细胞的异常增殖和新血管的形成。已证明伊曲康唑对治疗IH有效；然而，其作用的潜在机制仍不清楚。本研究的目的是检测伊曲康唑对血管瘤内皮细胞（HemECs）增殖、凋亡和血管生成的影响；以人脐静脉内皮细胞作为对照组。使用实时定量聚合酶链反应测定参与刺猬（HH）信号通路（SHH、PTCH1、SMO和GLI1）的基因表达。采用蛋白质印迹法测定相关蛋白的表达。在本研究中，伊曲康唑显著地剂量和时间依赖性抑制HemECs的活力。伊曲康唑抑制增殖细胞核抗原（PCNA）、Ki67和血管内皮生长因子（VEGF）的表达，表明该治疗抑制细胞增殖和血管生成。此外，伊曲康唑通过激活BAX的表达并抑制BCL2的表达诱导HemECs凋亡。伊曲康唑抑制SHH、PTCH1、SMO和GLI1的表达。重组人音猬因子（rhSHH）蛋白激活HH通路减弱了伊曲康唑对HemECs的作用。总之，伊曲康唑通过下调HH信号通路抑制HemECs的增殖、诱导凋亡并减少血管生成。因此，伊曲康唑可能是治疗IH的一种替代选择。
