Endoglin targeting inhibits tumor angiogenesis in non‐small cell lung cancer

Abstract

Endoglin, a transforming growth factor‐β co‐receptor, is highly expressed on angiogenic endothelial cells in many different solid tumors, including lung cancer. In patient samples, increased endoglin expression after the anti‐VEGF treatment was found. In contrast, in vitro TRC105, an endoglin‐neutralizing antibody, increased VEGF signaling in endothelial cells. This suggest that co‐administration with both endoglin antagonist and anti‐VEGF treatment may increase and sustain anti‐angiogenesis status. Subsequently, targeting endoglin is currently undertaken in clinical trials for anti‐angiogenic therapy. We aimed to explore how aspidin‐BB affected the endoglin expression and then effects on angiogenesis in lung cancer cells. Aspidin BB, a phloroglucinol derivative from Dryopteris fragrans (L.) Schott has been reported to demonstrate anticancer activity. In the present study, we investigated how aspidin‐BB affected the endoglin expression and then effects on angiogenesis. The binding mode of aspidin‐BB within the active site of endoglin was analyzed using DS 4.5. Our results showed that aspidin‐BB has strong affinity to endoglin. The results gave us a hint that aspidin‐BB could bind with endoglin and affected the BMP‐9, the main endoglin ligand, induced Alk1/Smad1 and/or Alk5/Smad2 phosphorylation in human umbilical vein endothelial cells (HUVECs). Further study will be focused on co‐administration with both endoglin antagonist and anti‐VEGF treatment, and determine its possibility to increase and sustain anti‐angiogenesis status.Support or Funding InformationThis work was supported by Grants from Ministry of Science and Technology (MOST 103‐2320‐B‐039‐026; MOST104‐2320‐B‐039‐007) and China Medical University (CMU105‐ASIA‐19;CMU106‐ASIA‐14).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.