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. 2020 Feb 19;10:2964. doi: 10.1038/s41598-020-59746-1

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© The Author(s) 2020

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Apatinib significantly suppressed angiogenesis of tumor cells in a dose-dependent manner (A–D). (A) The tube formation of HUVECs with different concentrations of Apatinib under normoxic or hypoxic conditions. (B) The number of junctions of each group. Apatinib could inhibit the HUVECs proliferation at a very low dose (0.1 uM), especially in the hypoxic environment, P > 0.05 in group A vs E and P < 0.05 in group B vs F, C vs G, D vs H. (C) The cell apoptosis rate of HUVECs with with different concentrations of Apatinib under normoxic or hypoxic conditions, P > 0.05 in group A vs E and P < 0.05 in group B vs F, C vs G, D vs H. (D) CD31 in VX2 tumor tissues was markedly inhibited by Apatinib in Day 3 (D3), the CD31 of group AI was lower than that of group I (P = 0.027 < 0.05). (E) Images of MVD in each group was shown by light microscopy (CD31 staining, 200×), a-Group AI, b-Group I, c-Group A and d-Group NS. Stripe and annular microvessels (black arrows) were observed in all the four groups, the MVD in Group AI was significantly lower than the other groups. Each point represents the mean ± SD (n = 3). *P < 0.05, ***P < 0.001.