Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma
Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatmen...
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PeerJ Inc.
2023-07-01
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| Online Access: | https://peerj.com/articles/15643.pdf |
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| author | Zhenyu Wang Yinxian Chen Lin Yang Dunbiao Yao Yang Shen |
| author_facet | Zhenyu Wang Yinxian Chen Lin Yang Dunbiao Yao Yang Shen |
| author_sort | Zhenyu Wang |
| collection | DOAJ |
| description | Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of β-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of β-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of β-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with β-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with β-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and β-elemene treatment alone groups. Our results suggest that β-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects. |
| first_indexed | 2024-03-09T06:53:58Z |
| format | Article |
| id | doaj.art-2ed008c513f8430896fd488612c851bc |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:53:58Z |
| publishDate | 2023-07-01 |
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| series | PeerJ |
| spelling | doaj.art-2ed008c513f8430896fd488612c851bc2023-12-03T10:08:47ZengPeerJ Inc.PeerJ2167-83592023-07-0111e1564310.7717/peerj.15643Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangiomaZhenyu Wang0Yinxian Chen1Lin Yang2Dunbiao Yao3Yang Shen4Department of Pediatric Orthopedics, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Pediatric Orthopedics, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaDepartment of Urinary Surgery, Cengong County People’s Hospital, Guizhou, ChinaDepartment of Orthopedics, Cengong County People’s Hospital, Guizhou, ChinaDepartment of Pediatric Orthopedics, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, ChinaHemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of β-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of β-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of β-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with β-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with β-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and β-elemene treatment alone groups. Our results suggest that β-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects.https://peerj.com/articles/15643.pdfβ-elemenePropranololHemangiomaProliferationAngiogenesis |
| spellingShingle | Zhenyu Wang Yinxian Chen Lin Yang Dunbiao Yao Yang Shen Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma PeerJ β-elemene Propranolol Hemangioma Proliferation Angiogenesis |
| title | Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma |
| title_full | Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma |
| title_fullStr | Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma |
| title_full_unstemmed | Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma |
| title_short | Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma |
| title_sort | combinative effects of β elemene and propranolol on the proliferation migration and angiogenesis of hemangioma |
| topic | β-elemene Propranolol Hemangioma Proliferation Angiogenesis |
| url | https://peerj.com/articles/15643.pdf |
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