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. 2019 Jun 26;9:545. doi: 10.3389/fonc.2019.00545

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Copyright © 2019 Roy, Guan, Liu and Zhang.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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RA inhibits VEGF secretion and endothelial cell-mediated angiogenesis in HCC. (A,B) HUVECs grown in the conditioned medium of RA-treated HepG2 cells produced shortened and severely broken 3D-tubular networks on the basement membrane matrix in a dose-dependent manner. (C) RA treatment abated VEGF release from HepG2 cells. Moreover, RA treatment also impeded the (D) migration and (E) invasion of HUVEC cells in a concentration-dependent manner. (F) RA modulated the expressions of AKT/mTOR and MAPK pathway molecules in the endothelial cells (n = 3 or more, 100× magnification, scale bar = 50 μm, **p ≤ 0.01 and *p ≤ 0.05 vs. control).