Effect of xanthohumol on proliferation, migration, tube formation and apoptosis of endothelial progenitor cells and its mechanism

doi:10.12307/2021.141

Abstract

Abstract: BACKGROUND: The development of tumor depends on angiogenesis to transport oxygen and micronutrients, and promote its metastasis. The neovessels in tumor is considered to be the new capillaries formed by the migration and proliferation of endothelial cells in the original vascular system. More and more evidence shows that bone marrow-derived endothelial progenitor cells contribute to neovascularization and have become an important target for anti-tumor therapy. In previous studies, there was no report about the effect of xanthohumol on bone marrow-derived endothelial progenitor cells.
OBJECTIVE: To study the effects of xanthohumol on the proliferation, migration, tube formation and apoptosis of bone marrow-derived endothelial progenitor cells, and to preliminarily explore its mechanism of action.
METHODS: The third passage of bone marrow-derived endothelial progenitor cells were divided into four groups: 5, 10, 20 μmol/L xanthohumol group and the same amount of dimethyl sulfoxide solution as the control group. After intervention for 24 and 48 hours, effect of xanthohumol on the proliferation of bone marrow-derived endothelial progenitor cells was measured by the CCK-8 method. After intervention for 24 hours, the scratch test and the Transwell test were used to detect the effect of xanthohumol on the migration of mouse bone marrow-derived endothelial progenitor cells. After intervention for 6 hours, the tube test was used to detect the effect of xanthohumol on the lumen formation of mouse bone marrow-derived endothelial progenitor cells. After intervention for 48 hours, flow cytometry and TUNEL assay were applied to detect the effect of xanthohumol on the apoptosis of mouse bone marrow-derived endothelial progenitor cells. After intervention for 48 hours, western blot assay was employed to detect the effect of xanthohumol on vascular endothelial growth factor, vascular endothelial growth factor receptor 2, P65 and p-P65 protein.
RESULTS AND CONCLUSION: (1) After the intervention of xanthohumol, the half maximal inhibitory concentration (IC50) of bone marrow-derived endothelial progenitor cells at 24 and 48 hours were (22.19±0.98) and (11.51±1.25) μmol/L, respectively. The comparison between them was statistically significant (P < 0.05), indicating that xanthohumol could significantly inhibit the proliferation of bone marrow-derived endothelial progenitor cells in a certain dose-effect relationship (P < 0.05). (2) Compared with the control group, as the concentration of xanthohumol increases, the scratches were more obvious (P < 0.05), and the number of migrating cells decreased gradually (P < 0.05). (3) A large number of tubule-like structures were formed in the control group, while the tubule-like structures were significantly reduced in the 5 and 10 μmol/L xanthohumol groups, and no tubule-like structures were formed in the 20 μmol/L xanthohumol group, with significant difference compared with the control group (P < 0.05). (4) The apoptosis rate was significantly increased after xanthohumol treatment in a concentration-dependent manner, and the apoptosis rate in each xanthohumol group was significantly higher than that in the control group (P < 0.05). (5) Compared with the control group, with the increase of xanthohumol concentration, the expression of p-P65 and vascular endothelial growth factor decreased, while vascular endothelial growth factor receptor 2 increased in a concentration-dependent manner (P < 0.05). (6) These results indicate that xanthohumol can inhibit the proliferation, migration, tube formation and apoptosis of bone marrow-derived endothelial progenitor cells. The mechanism may be through the inhibition of NF-κB/vascular endothelial growth factor signaling pathway, indicating that xanthohumol has the potential of anti-tumor angiogenesis.

Key words: bone marrow, endothelial progenitor cells, xanthohumol, vascular endothelial progenitor cells, angiogenesis, NF-κB, signaling pathway

CLC Number:

Tan Xiaowu, Yu Xiaofan, Jiang Huijiao, Xing Zhikun, Zhao Xueyuan, Gao Fengyi, Wu Xiangwei, Chen Xueling. Effect of xanthohumol on proliferation, migration, tube formation and apoptosis of endothelial progenitor cells and its mechanism[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(31): 4988-4994.

Figures/Tables 8

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