1. Academic Validation
  2. Sulfated fucoidan FP08S2 inhibits lung cancer cell growth in vivo by disrupting angiogenesis via targeting VEGFR2/VEGF and blocking VEGFR2/Erk/VEGF signaling

Sulfated fucoidan FP08S2 inhibits lung cancer cell growth in vivo by disrupting angiogenesis via targeting VEGFR2/VEGF and blocking VEGFR2/Erk/VEGF signaling

  • Cancer Lett. 2016 Nov 1;382(1):44-52. doi: 10.1016/j.canlet.2016.08.020.
Huanjun Chen 1 Qifei Cong 1 Zhenyun Du 1 Wenfeng Liao 1 Lei Zhang 1 Yanli Yao 1 Kan Ding 2
Affiliations

Affiliations

  • 1 Glycochemistry and Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China.
  • 2 Glycochemistry and Glycobiology Lab, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China; University of Chinese Academy of Sciences, No.19A Yuquan Road, Beijing 100049, China. Electronic address: [email protected].
Abstract

Fucoidan may inhibit angiogenesis. However, its functional target molecule and the underlying mechanism are still vague. In the present study, we showed that sulfated fucoidan FP08S2 from Sargassum fusiforme inhibited tube formation as well as migration and invasion of human microvascular endothelial cells (HMEC-1). In addition, FP08S2 was confirmed to disrupt VEGF-induced angiogenesis both in vitro and in vivo. Further study indicated that FP08S2 could bind to both VEGF and VEGFR2/KDR/Flk-1 to interfere with VEGF-VEGFR2 interaction. Moreover, VEGFR2/KDR/Flk-1/ERK/VEGF signaling pathway was blocked by FP08S2 in HMEC-1 cells. Importantly, FP08S2 impeded the growth and microvessel formation of A549 Cancer cell xenograft in nude mice. These results suggested that FP08S2 presented remarkable anti-angiogenic activity via blocking VEGF signaling and could be a potential novel leading compound to inhibit lung Cancer cell growth.

Keywords

Angiogenesis; Fucoidan; Lung cancer; VEGF.

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