DCZ3301, an aryl-guanidino agent, inhibits ocular neovascularization via PI3K/AKT and ERK1/2 signaling pathways

  • Exp Eye Res. 2020 Dec;201:108267. doi: 10.1016/j.exer.2020.108267.
Kai Xu  1 ,  Bo Li  2 ,  Shujie Zhang  1 ,  Fangyuan Hu  1 ,  Zhijian Xu  2 ,  Lei Li  1 ,  Yihan Zhang  1 ,  Weiliang Zhu  3 ,  Chen Zhao  4
Affiliations
  • 1. Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, And Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, China.
  • 2. CAS Key Laboratory of Receptor Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • 3. CAS Key Laboratory of Receptor Research; Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. Electronic address: [email protected].
  • 4. Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, And Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, China. Electronic address: [email protected].
PMID: 32986979 DOI: 10.1016/j.exer.2020.108267
Abstract

Neovascularization is a critical process in the pathophysiology of neovascular eye diseases. Although anti-VEGF therapy has achieved remarkable curative effects, complications, limited efficacy and drug resistance remain the prominent problems. DCZ3301, an aryl-guanidino compound, was reported to have anti-tumor activity in the previous studies. Here, we demonstrated the effects of DCZ3301 on human umbilical vein endothelial cell (HUVEC) in vitro, and performed choroid microvascular sprouting assay ex vivo and alkali-burn induced corneal neovascularization mouse model in vivo. We found that DCZ3301 inhibited the proliferation, migration, and tube formation of HUVECs, while inducing the spontaneous Apoptosis of HUVECs by suppressing the activation of PI3K/Akt and ERK1/2 pathways. Furthermore, DCZ3301 inhibited the choroid microvascular sprouting, diminished the area of corneal neovascularization and attenuated the edema of corneal stroma after alkali burn. Together, these results suggested that DCZ3301 exerted anti-angiogenic properties, and might be regarded as a potential candidate for ocular neovascularization.

Keywords
Apoptosis; Choroid microvascular sprouting; Corneal neovascularization; DCZ3301; ERK1/2 pathway; PI3K/AKT pathway.
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