Propranolol is the first-line drug for treatment of infantile hemangioma. However, its mechanism of action remains unclear. Nuclear factor-κB is highly expressed in tumors, directly or indirectly promoting angiogenesis. Thrombospondin-1 is the most important antiangiogenesis protein in vivo. These proteins mediate signaling pathways, probably playing an important role in hemangioma treatment. This study explored the synergistic regulation of thrombospondin-1 and nuclear factor-κB signaling pathways in the treatment of hemangioma with propranolol.
The hemangioma-derived endothelial cells were sorted out from the specimens of proliferative hemangioma by flow cytometry. Furthermore, a BALB/c nude mouse hemangioma model was established. Viability and proliferation of hemangioma-derived endothelial cells and the role of thrombospondin-1 and nuclear factor-κB signaling pathways were observed after propranolol administration in vitro and in vivo.
The expression of thrombospondin-1 and its receptor CD36 in hemangioma-derived endothelial cells gradually increased with the increase in propranolol concentration, whereas the expression of nuclear factor-κBp65, phosphorylated inhibitor of κB alpha (p-IκBα), and phosphorylated inhibitor of nuclear factor-κB kinase beta (p-IκKβ) weakened gradually (p < 0.05). In vivo, the tumors shrank gradually after propranolol treatment, with an increase in thrombospondin-1 and CD36 and a decrease in nuclear factor-κBp65, p-IκBα, and p-IκKβ (p < 0.05). Glucocorticoid improved the antiangiogenesis mediated by thrombospondin-1/CD36 and inhibited the angiogenesis mediated by nuclear factor-κB/IκB (p < 0.05). Negative regulation occurred between the two signaling pathways.
The treatment of infantile hemangioma with propranolol is promising to promote thrombospondin-1–mediated antiangiogenesis and to block nuclear factor-κB–mediated angiogenesis.
Shijiazhuang, Hebei, People’s Republic of China
From the Departments of Pediatric Surgery and Central Laboratory, Second Hospital of Hebei Medical University.
Received for publication May 16, 2017; accepted February 27, 2018.
Presented in part at the 12th Annual Conference of the Chinese Society of Pediatric Surgery, Xi’an City, Shanxi Province, China, September 8-10, 2016.
Disclosure:None of the authors has a financial interest in any of the products, devices, or drugs mentioned in this article.
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Weili Xu, M.D., Ph.D., Department of Pediatric Surgery, Second Hospital of Hebei Medical University, Shijiazhuang 050000, People’s Republic of China, email@example.com