Abstract | BACKGROUND: Oral propranolol (PRN) has recently been shown to be highly effective for infantile hemangiomas (IHs), and is currently recommended as the first-line treatment of complicated IHs. However, the therapeutic mechanism(s) still remain unclear. METHODS: In this study, we tested hemangioma-derived stem cells for expression of vascular endothelial growth factor ( VEGF) in vitro and studied the inhibition of VEGF expression. We used PCR, Elisa, Western blotting and immunohistochemistry in vivo and in vitro trial. RESULTS: The study demonstrated that application of PRN at a "normal" concentration equivalent to plasma concentration did not inhibit proliferation or promote apoptosis of hemangioma derived stem cells (HemSCs) isolated from IH patients. PRN suppressed expression of vascular endothelial growth factor ( VEGF) and basic Fibroblast Growth Factor (bFGF) in HemSCs in vitro. Morphological, histological and immunohistological improvement were observed in vivo using murine IH model in which HemSCs pre-treated with PRN were implanted into BALB/c-nu mice. In the pre-treated HemSC grafts, mean micro-vessel density (MVD) significantly decreased and protein levels of VEGF markedly decreased, while bFGF was still detectable. CONCLUSIONS: The results suggested PRN inhibited angiogenesis via down-regulating the expression of vascular endothelial growth factor in hemangioma derived stem cell. These findings provide critical insight into the potential mechanisms of PRN action on IH.
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Authors | Ling Zhang, Hua-Ming Mai, Jing Zheng, Jia-Wei Zheng, Yan-An Wang, Zhong-Ping Qin, Ke-Lei Li |
Journal | International journal of clinical and experimental pathology
(Int J Clin Exp Pathol)
Vol. 7
Issue 1
Pg. 48-55
( 2014)
ISSN: 1936-2625 [Electronic] United States |
PMID | 24427325
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiogenesis Inhibitors
- Vascular Endothelial Growth Factor A
- Propranolol
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Topics |
- Angiogenesis Inhibitors
(pharmacology)
- Animals
- Apoptosis
(drug effects)
- Blotting, Western
- Cell Proliferation
(drug effects)
- Cells, Cultured
- Down-Regulation
(drug effects)
- Enzyme-Linked Immunosorbent Assay
- Hemangioma
(metabolism, pathology)
- Humans
- Immunohistochemistry
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplastic Stem Cells
(drug effects, metabolism)
- Neovascularization, Pathologic
(metabolism)
- Propranolol
(pharmacology)
- Reverse Transcriptase Polymerase Chain Reaction
- Vascular Endothelial Growth Factor A
(biosynthesis)
- Xenograft Model Antitumor Assays
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