Objective To investigate the effects of propranolol on the proliferation, apoptosis, migration, and tube formation ability of human umbilical vein endothelial cells (HUVEC), as well as its impact on the expression of sex-determining region Y-box 18 (SOX18), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor A (VEGFA). Methods HUVEC were treated with different concentrations of propranolol, and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration. The experiment consisted of a control group and groups treated with different concentrations of propranolol (50, 100, 150 μmol/L). Apoptosis, migration, and tube formation of HUVEC were observed using flow cytometry, wound healing assays, and tube formation assays. Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA. Results Compared to the control group, the apoptosis rate in the propranolol treatment groups increased significantly (P<0.05), and it rose significantly with increasing drug concentration (P<0.05). The wound healing rate decreased in the propranolol treatment groups, and both the number of tube formation nodes and total tube length were reduced (P<0.05). The expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups (P<0.05). Conclusions Propranolol can inhibit the proliferation, migration, and tube formation ability of HUVEC and promote cell apoptosis, resulting in decreased expression levels of SOX18, MMP-7, and VEGFA.
Key words
Propranolol /
Infantile hemangioma /
Sex-determining region Y-box 18 /
Matrix metalloproteinase-7 /
Vascular endothelial growth factor A /
Human umbilical vein endothelial cell
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References
1 Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy[J]. N Engl J Med, 2008, 358(24): 2649-2651. PMID: 18550886. DOI: 10.1056/NEJMc0708819.
2 Krowchuk DP, Frieden IJ, Mancini AJ, et al. Clinical practice guideline for the management of infantile hemangiomas[J]. Pediatrics, 2019, 143(1): e20183475. PMID: 30584062. DOI: 10.1542/peds.2018-3475.
3 Smithson SL, Rademaker M, Adams S, et al. Consensus statement for the treatment of infantile haemangiomas with propranolol[J]. Australas J Dermatol, 2017, 58(2): 155-159. PMID: 28251611. DOI: 10.1111/ajd.12600.
4 Solman L, Glover M, Beattie PE, et al. Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines[J]. Br J Dermatol, 2018, 179(3): 582-589. PMID: 29774538. DOI: 10.1111/bjd.16779.
5 郑家伟, 王绪凯, 秦中平, 等. 口服普萘洛尔治疗婴幼儿血管瘤中国专家共识（2022版）[J]. 中国口腔颌面外科杂志, 2022, 20(4): 313-319. DOI: 10.19438/j.cjoms.2022.04.001.
6 Grimm D, Bauer J, Wise P, et al. The role of SOX family members in solid tumours and metastasis[J]. Semin Cancer Biol, 2020, 67(Pt 1): 122-153. PMID: 30914279. DOI: 10.1016/j.semcancer.2019.03.004.
7 Olbromski M, Podhorska-Oko?ów M, Dzi?giel P. Role of the SOX18 protein in neoplastic processes[J]. Oncol Lett, 2018, 16(2): 1383-1389. PMID: 30008814. PMCID: PMC6036441. DOI: 10.3892/ol.2018.8819.
8 Chen Q, Jin M, Yang F, et al. Matrix metalloproteinases: inflammatory regulators of cell behaviors in vascular formation and remodeling[J]. Mediators Inflamm, 2013, 2013: 928315. PMID: 23840100. PMCID: PMC3694547. DOI: 10.1155/2013/928315.
9 Ito TK, Ishii G, Saito S, et al. Degradation of soluble VEGF receptor-1 by MMP-7 allows VEGF access to endothelial cells[J]. Blood, 2009, 113(10): 2363-2369. PMID: 18974372. DOI: 10.1182/blood-2008-08-172742.
10 Kilcline C, Frieden IJ. Infantile hemangiomas: how common are they? A systematic review of the medical literature[J]. Pediatr Dermatol, 2008, 25(2): 168-173. PMID: 18429772. DOI: 10.1111/j.1525-1470.2008.00626.x.
11 Munden A, Butschek R, Tom WL, et al. Prospective study of infantile haemangiomas: incidence, clinical characteristics and association with placental anomalies[J]. Br J Dermatol, 2014, 170(4): 907-913. PMID: 24641194. PMCID: PMC4410180. DOI: 10.1111/bjd.12804.
12 Lamy S, Lachambre MP, Lord-Dufour S, et al. Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells[J]. Vascul Pharmacol, 2010, 53(5-6): 200-208. PMID: 20732454. DOI: 10.1016/j.vph.2010.08.002.
13 Ford JR, Gonzalez-Barlatay J, Valenzuela AA. Early orbital infantile hemangioma that emphasizes the importance of glucose-transporter-1 (GLUT-1)[J]. Can J Ophthalmol, 2018, 53(2): e58-e60. PMID: 29631842. DOI: 10.1016/j.jcjo.2017.07.003.
14 Harbi S, Park H, Gregory M, et al. Arrested development: infantile hemangioma and the stem cell teratogenic hypothesis[J]. Lymphat Res Biol, 2017, 15(2): 153-165. PMID: 28520518. DOI: 10.1089/lrb.2016.0030.
15 罗勇奇, 曾迎红, 胡梦叶, 等. 普萘洛尔对体外培养血管瘤内皮细胞的影响及其分子机制[J]. 中华皮肤科杂志, 2017, 50(11): 800-805. DOI: 10.3760/cma.j.issn.0412-4030.2017.11.006.
16 Liu ZL, Chen HH, Zheng LL, et al. Angiogenic signaling pathways and anti-angiogenic therapy for cancer[J]. Signal Transduct Target Ther, 2023, 8(1): 198. PMID: 37169756. PMCID: PMC10175505. DOI: 10.1038/s41392-023-01460-1.
17 Eelen G, Treps L, Li X, et al. Basic and therapeutic aspects of angiogenesis updated[J]. Circ Res, 2020, 127(2): 310-329. PMID: 32833569. DOI: 10.1161/CIRCRESAHA.120.316851.
18 Villani R, Sim SL, Roy E, et al. Ectopic expression of SOX18 in basal cell carcinoma negatively regulates tumour progression[J]. J Dermatol Sci, 2020, 98(3): 179-185. PMID: 32444239. DOI: 10.1016/j.jdermsci.2020.04.006.
19 Chen J, Feng W, Sun M, et al. TGF-β1-induced SOX18 elevation promotes hepatocellular carcinoma progression and metastasis through transcriptionally upregulating PD-L1 and CXCL12[J]. Gastroenterology, 2024, 167(2): 264-280. PMID: 38417530. DOI: 10.1053/j.gastro.2024.02.025.
20 钱世宁, 朱小飞, 季明德, 等. 含人SOX18基因真核表达载体的构建及其重组蛋白诱导血管内皮细胞增殖的研究[J]. 南京医科大学学报（自然科学版）, 2018, 38(2): 166-170. DOI: 10.7655/NYDXBNS20180205.
21 石俊强, 王建礼, 王国芳, 等. 转录因子性别决定区Y框18对子宫颈癌HeLa细胞增殖、迁移和侵袭的影响[J]. 肿瘤研究与临床, 2017, 29(6): 370-373. DOI: 10.3760/cma.j.issn.1006-9801.2017.06.003.
22 Laronha H, Caldeira J. Structure and function of human matrix metalloproteinases[J]. Cells, 2020, 9(5): 1076. PMID: 32357580. PMCID: PMC7290392. DOI: 10.3390/cells9051076.
23 Greenlee KJ, Werb Z, Kheradmand F. Matrix metalloproteinases in lung: multiple, multifarious, and multifaceted[J]. Physiol Rev, 2007, 87(1): 69-98. PMID: 17237343. PMCID: PMC2656382. DOI: 10.1152/physrev.00022.2006.
24 Raffetto JD, Khalil RA. Matrix metalloproteinases and their inhibitors in vascular remodeling and vascular disease[J]. Biochem Pharmacol, 2008, 75(2): 346-359. PMID: 17678629. PMCID: PMC2254136. DOI: 10.1016/j.bcp.2007.07.004.
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