Epigallocatechin-3-gallate inhibits tumor angiogenesis: involvement of endoglin/Smad1 signaling in human umbilical vein endothelium cells - 13/11/19
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Graphical abstract |
As the redundancy between endoglin and VEGF signaling in angiogenesis were confirmed. Increased endoglin signaling was found in a semaxanib-treated HUVECs; and vice versa in endothelial cells. Our results showed that combined targeting of the endoglin and VEGF pathway significantly increased antiangiogenic effects in vitro.
Highlights |
• | Combined targeting to endoglin and VEGF increase antiangiogenic effects. |
• | EGCG significantly inhibited endoglin upregulation after semaxanib-treated HUVECs. |
• | EGCG signicantly decreased the semantinib-induced endoglin overexpression. |
• | Combines EGCG with semaxanib overcome drug resistance. |
Abstract |
Strategies targeting endoglin are currently being investigated in clinical trials as an anti-angiogenic therapy. The redundancy between endoglin and vascular endothelial growth factor (VEGF) signaling in angiogenesis was verified. Increased endoglin signaling after an anti-VEGF treatment was observed in patients. Treatment with an endoglin-neutralizing antibody increased VEGF signaling in endothelial cells. Therefore, strategies targeting both the endoglin and VEGF pathways were applied to determine whether the anti-angiogenic effects were increased in vitro. Five possible hits for endoglin were identified from 2000 compounds in the Traditional Chinese Medicine Database using Discovery Studio 4.5 Epigallocatechin-3-gallate (EGCG) attenuates angiogenesis by downregulating VEGF; however, researchers have not determined whether its anti-angiogenic effects are mediated by endoglin/Smad1 signaling. A major contribution of this study is that EGCG significantly inhibited the upregulation of endoglin in semaxanib-treated human umbilical vein endothelial cell. Thus, a combination treatment with EGCG and a VEGF tyrosine kinase inhibitor would be appropriate to reverse drug resistance. EGCG alone significantly decreased endoglin/pSmad1 levels in HUVECs. In the angiogenesis assay, the migration, invasion, and tube formation of HUVECs were markedly suppressed by higher concentrations of EGCG. A combination treatment with EGCG and semaxanib further produced increased anti-angiogenic effects. The main contribution of the study indicated that EGCG significantly decreased the semaxanib-induced overexpression of endoglin. Therefore, a combination treatment including EGCG will probably solve the drug resistance to anti-VEGF treatments.
Le texte complet de cet article est disponible en PDF.Keywords : EGCG, VEGF, Endoglin, Smad1, Angiogenesis
Plan
Vol 120
Article 109491- décembre 2019 Retour au numéro
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