Abstract
Lycium barbarum polysaccharide (LBP) has a variety of pharmacological and biological activities such as anti-inflammatory, antioxidation, anti-apoptosis, immune regulation and other pharmacological effects; however, the effect of LBP on infantile hemangioma (IH) was less reported. Primary human hemangioma endothelial cells (HemECs) were isolated from fresh surgical specimens of patients. HemECs was treated with LBP and the changes in proliferative and apoptotic signaling pathways were investigated by performing cell counting kit-8, cloning formation experiment, in vitro angiogenesis experiment, flow cytometry, Western blot, immunofluorescence, HE stain and real-time quantitative polymerase chain reaction. We found that LBP potently inhibited the proliferation of HemECs and achieved a low-micromolar IC50 (45 and 40 μg/ml, the half maximal inhibitory concentration) value and less angiogenesis, however, the IC50 had no effect on human umbilical vein endothelial cells (HUVECs) viability. LBP treatment induced apoptosis in HemECs, which was supported by positive Annexin-V-FITC staining, the activation of cleaved caspase-3 and Bcl-2-associated X protein (Bax) and the inhibition of B-cell lymphoma/leukemia-2 (Bcl-2). Moreover, the result demonstrated that LBP suppressed the expressions of proliferating cell nuclear antigen (PCNA), Ki67, vascular endothelial growth factor (VEGF), VEGFR2 and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signal pathway. PI3K-specific agonist (IGF-1) had promotive effects on HemECs proliferation, which was reversed by LBP. Our study suggests that the effectiveness of LBP in IHs may be associated with its potent anti-proliferative and apoptotic activities in HemECs. Thus, our findings may provide an effective medicine for IHs treatment.
Highlights
Infantile hemangioma (IH) is the most frequent benign tumor in infants and young children, and the incidence of IH is approximately 3–10% [1]
We found that Lycium barbarum polysaccharide (LBP) potently inhibited the proliferation of hemangioma endothelial cell (HemEC) and achieved a low-micromolar IC50 (45 and 40 μg/ml, the half maximal inhibitory concentration) value and less angiogenesis, the IC50 had no effect on human umbilical vein endothelial cells (HUVECs) viability
To verify that the cells isolated from IH tissue were HemECs, the expressions of factor VIII, CD31 and CD34 in the cells were examined by immunofluorescent staining
Summary
Infantile hemangioma (IH) is the most frequent benign tumor in infants and young children, and the incidence of IH is approximately 3–10% [1]. Caucasians, low-weight premature infants, multiple births and elder infants are more susceptible to have the disease [2]. Potential complications of IH are, for example, permanent disfigurement, ulcers, scarring, bleeding, visual impairment, airway obstruction, congestive heart failure, in some cases, IH could even cause death [3]. 10% of all IH cases complete their own degradation within 1 year, while the remaining 90% IH cases take 3–10 years or longer to degrade [4]. Most of regressed tumors leave a mark that affects aesthetics or fibrous fat deposits [5]. Researchers tend to actively intervene in the early stage of IH to promote and accelerate the License 4.0 (CC BY)
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