普萘洛尔通过抑制 HUVECs 的增殖、迁移、侵袭和管腔形成参与婴儿血管瘤的治疗。
Propranolol Participates in the Treatment of Infantile Hemangioma by Inhibiting HUVECs Proliferation, Migration, Invasion, and Tube Formation.
机构信息
Department of Stomatology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, China.
出版信息
Biomed Res Int. 2021 Jan 27;2021:6636891. doi: 10.1155/2021/6636891. eCollection 2021.
OBJECTIVE
Infantile hemangiomas (IHs) are the most common benign tumors in infancy. The purpose of this study was to study the effects of propranolol on the function of human umbilical vein endothelial cells (HUVECs), in order to preliminarily elucidate the mechanism of propranolol in the treatment of IHs.
METHODS
HUVECs were treated with different concentrations of propranolol (30 M, 60 M, 90 M, and 120 M) with or without VEGF. Their proliferation, migration, invasion, adhesion, and tube formation ability were tested by using CCK-8, wound healing assay, transwell, cell adhesion assay, and tube formation assay. The expressions of HUVECs angiogenesis signaling molecules pERK/ERK, pAKT/AKT, p-mTOR/mTOR, and pFAK/FAK were detected by Western blot.
RESULTS
Compared with the control group, propranolol could significantly inhibit the proliferation, migration, invasion, adhesion, and tube formation of HUVECs. Further studies showed that it could not only inhibit the migration, invasion, and tube formation ability of HUVECs after VEGF induction but also inhibit the phosphorylated protein expressions of angiogenesis-related signaling molecules like AKT, mTOR, ERK, and FAK in HUVECs, with a concentration-dependent inhibitory effect.
CONCLUSION
Propranolol can inhibit the proliferation, migration, invasion, adhesion, and tube formation of hemangioma endothelial cells; block VEGF-mediated angiogenesis signaling pathway; suppress the expressions of downstream angiogenesis-related signaling molecules; and ultimately achieve the effect of treatment of IHs.
目的
婴幼儿血管瘤（IHs）是婴儿期最常见的良性肿瘤。本研究旨在研究普萘洛尔对人脐静脉内皮细胞（HUVECs）功能的影响，以期初步阐明普萘洛尔治疗 IHs 的机制。
方法
用不同浓度的普萘洛尔（30μM、60μM、90μM 和 120μM）处理 HUVECs，或用或不用 VEGF。通过 CCK-8 法、划痕愈合实验、Transwell 实验、细胞黏附实验和管形成实验检测 HUVECs 的增殖、迁移、侵袭、黏附和管形成能力。通过 Western blot 检测 HUVECs 血管生成信号分子 pERK/ERK、pAKT/AKT、p-mTOR/mTOR 和 pFAK/FAK 的表达。
结果
与对照组相比，普萘洛尔可显著抑制 HUVECs 的增殖、迁移、侵袭、黏附和管形成。进一步的研究表明，它不仅可以抑制 VEGF 诱导后的 HUVECs 的迁移、侵袭和管形成能力，还可以抑制 HUVECs 中与血管生成相关的信号分子如 AKT、mTOR、ERK 和 FAK 的磷酸化蛋白表达，具有浓度依赖性抑制作用。
结论
普萘洛尔可抑制血管瘤内皮细胞的增殖、迁移、侵袭、黏附和管形成；阻断 VEGF 介导的血管生成信号通路；抑制下游与血管生成相关的信号分子的表达；最终达到治疗 IHs 的效果。
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